journal of endodontics

Pulp Symposium S1 AAE and AAPD Symposium Overview: Emerging Science in Pulp Therapy—New Insights Into Dilemmas and ControversiesGerald N. Glickman and N. Sue Seale

S2 The Caries Process and Its Effect on the Pulp: The Science Is Changing andSo Is Our UnderstandingLars Bjørndal

S6 Diagnosis Dilemmas in Vital Pulp Therapy: Treatment for the Toothache IsChanging, Especially in Young, Immature TeethJoe H. Camp

S13 Regenerative Potential of Dental PulpMartin Trope

S18 Vital Pulp Therapy with New Materials for Primary Teeth: New Directions andTreatment PerspectivesAnna B. Fuks

S25 Vital Pulp Therapy with New Materials: New Directions and TreatmentPerspectives—Permanent TeethDavid E. Witherspoon

S29 Indirect Pulp Therapy and Stepwise ExcavationLars Bjørndal

S34 Indirect Pulp Capping and Primary Teeth: Is the Primary Tooth PulpotomyOut of Date?James A. Coll

S40 Is Formocresol Obsolete? A Fresh Look at the Evidence Concerning Safety IssuesAlan R. Milnes

S47 “New Age” Pulp Therapy: Personal Thoughts on a Hot DebatePaula Jane Waterhouse

S51 Regeneration Potential of the Young Permanent Tooth: What Does the FutureHold?Kenneth M. Hargreaves, Todd Geisler, Michael Henry, and Yan Wang

S57 Contemporary Perspectives on Vital Pulp Therapy: Views From the Endodontistsand Pediatric DentistsN. Sue Seale and Gerald N. Glickman

Journal of EndodonticsJuly 2008, Volume 34, Number 7S

AAE and AAPD Symposium Overview: Emerging Sciencein Pulp Therapy—New Insights Into Dilemmas andControversies

Evidence-based best practices are yet to be established for themanagement of caries-associated pulpal disease in young perma-nent and primary teeth. Controversies still remain among practi-

tioners, including pediatric dentists and endodontists, as to which treat-ment modalities are most predictable in the contemporary practice ofpulp therapy. Many clinicians still remain divided as to whether indirectpulp capping is a viable procedure in primary and young permanentteeth, or whether formocresol remains the medicament of choice forpulpotomies in primary teeth. To begin the process of establishing evi-dence-based best practices in pulpal therapy as well as highlight some ofthe future directions in pulp therapy including pulp regeneration withstem cells and root canal revascularization, the American Academy ofPediatric Dentistry (AAPD) and the American Association of Endodon-tists (AAE) jointly sponsored “Emerging Science in Pulp Therapy: NewInsights into Dilemmas and Controversies.” The symposium was held onNovember 2–3, 2007, in Chicago, Illinois.

The convening of this pulp therapy symposium was heralded as amajor event in that it was a first time conjoint symposium sponsored bythese 2 national specialty organizations. The genesis of the idea for jointsponsorship was the need to examine the shared procedures performedby the 2 specialties. With specialty organizations routinely producingevidence-based practice guidelines that provide the foundation fortreatments performed, it is critical that when 2 specialties perform thesame or similar treatments, their guidelines are parallel in language andin content. Without these guidelines, confusion and uncertainty willresult in clinical practice when a rational treatment plan is required tomanage a specific pathologic entity such as caries.

Pediatric dentistry and endodontics share in the important treat-ment decisions associated with pulpal therapy for the cariously involvedyoung permanent tooth. In addition, endodontists are consultants toand involved in pulp therapy treatment decisions for the cariously in-volved primary tooth. With the eventual expectation that the 2 organi-zations could come together and produce practice guidelines that sharecommon goals and language for caries-associated pulp therapy for pri-mary and young permanent teeth, the decision was made to bring to-gether a panel of world-renown experts from both specialties to presentthe current best evidence as a first step in developing the anticipatedguidelines.

Individuals identified to be on the planning committee from theAAE were Drs Gerald N. Glickman, Alan Gluskin, and Bradford Johnson.From the AAPD, Drs Suzi Seale, Elizabeth Barr, and James Coll wereselected. These individuals met and identified the following areas asappropriate for focus: the nature of the carious lesion of dentin; indirectpulp therapy, including stepwise excavation for both young permanentteeth and primary teeth; primary tooth pulpotomy agents with specialemphasis on formocresol and the controversy surrounding its use; andrevascularization of young permanent teeth and pulpal regeneration byusing stem cells. To that end, a cadre of 9 experts was identified andinvited to present evidence for assigned topics. The articles resultingfrom their presentations appear in this publication.

During the conference Professor Lars Bjørndal discussed the car-ies process and its effect on the pulp. He applied this information to thedilemma of the deep carious lesion and indirect pulp capping, withspecial emphasis on the coronal seal. Dr Joe Camp focused on diagnos-tic dilemmas in vital pulp therapy for young immature teeth. Dr MartinJ. Trope spoke on how new trends are changing our understanding ofthe regenerative potential of the dental pulp, whereas Dr David Wither-spoon spoke on new directions and treatment perspectives involvingpulpal revascularization for permanent teeth. Dr Anna Fuks presented acompilation of the evidence for different pulpotomy agents in treatingthe vital cariously involved primary tooth. Dr Jim Coll provided infor-mation about indirect pulp capping for primary teeth as an alternative topulpotomy. Drs Alan Milnes and P. J. Waterhouse presented opposingviews about the controversy over formocresol as a pulpotomy agent forhuman teeth. Finally, Dr Ken Hargreaves provided evidence for thefuture of pulpal regeneration for the young permanent tooth.

Because 2 specialty groups were represented, the planning com-mittee sought to determine, through a brief pretest completed before thefirst speaker, the baseline opinions of the audience about the varioustopics to be presented. After the last speaker, a more lengthy set ofquestions about the same topics were presented to the audience fortheir opinions by using an audience response system. Attendees’ re-sponses were identified by specialty, and the results of the comparisonsof the presymposium and postsymposium opinions within specialty andacross specialties are also presented in this publication.

We believe this symposium represented an important landmark inbringing together different disciplines with potentially different opin-ions to reach an evidence-based consensus about common treatmentdilemmas. Because practice guidelines increasingly drive our treatmentdecisions, it is important that we are in agreement about their content,ultimately for the care and benefit of our patients.

Gerald N. Glickman, DDS, MSVice-President, American Association of Endodontists

andProfessor and Chairman, Department of Endodontics

Baylor College of DentistryTexas A&M University Health Science Center

Dallas, Texas

N. Sue Seale, DDS, MSDRegents Professor and Chairman, Department of Pediatric Dentistry

Baylor College of DentistryTexas A&M University Health Science Center

Dallas, Texas

Conflict of Interest: Gerald N. Glickman, DDS, MS, reports no financialinterests or potential conflicts of interest. N. Sue Seale, DDS, MSD, reports nofinancial interests or potential conflicts of interest.

Copyright © 2008 American Academy of Pediatric Dentistry and AmericanAssociation of Endodontists.

This article is being published concurrently in Pediatric Dentistry, May/June2008; Volume 30, Issue 3. The articles are identical. Either citation can be usedwhen citing this article.doi:10.1016/j.joen.2008.02.036

Pulp Symposium

JOE — Volume 34, Number 7S, July 2008 AAE and AAPD Symposium Overview S1

The Caries Process and Its Effect on the Pulp: The ScienceIs Changing and So Is Our UnderstandingLars Bjørndal, DDS, PhD

AbstractThe understanding of the caries process and its effecton the pulp is presented in the context that caries doesdevelop in various rates of progression. Early in thecaries process, the pulp reflects changes within lesionactivity. Thus, the early pulp response is reversible.Later, the rate of caries progression is reflected by thequality of the tertiary dentin. Slowly progressing lesionscreate tertiary dentin resembling normal tubular dentin.Rapidly progressing lesions lead to the production ofatubular dentin or complete absence of tertiary dentin,as well as pulp necrosis and apical pathology. Finally,the nature of the untreated deep carious lesion is anecosystem that might undergo significant changes. Theuntreated lesion is temporarily converted from an activeand closed lesion environment into one that is openand slowly progressing. The analysis of untreated car-ious lesions has transformed the treatment philosophyof deep carious lesions. (J Endod 2008;34:S2-S5)

Key WordsDental caries, dental pulp, dentin, indirect pulp treat-ment, stepwise excavation, tertiary dentin

Can We Obtain Consensus on Caries Pathology?Caries can be compared with a train that passes through many stations. Imagine

that each station represents a specific stage of caries progression. The first stationrepresents the initial surface etching at the outer enamel layer, leading to the dull whiteappearance of the active progressing enamel lesion. The last station represents the deepestlayer of the carious tooth, with a necrotic, infected root canal system and the presence ofapical pathosis. Investigators, clinicians, and researchers who enter the “caries train” havetypically focused on only a few stations. They might also have different understandingsand opinions about how to treat dental caries. Their opinions have developed from amixture of clinical empirical tradition and an understanding from research. Theseopinions could be named the cariologist opinion, the operative opinion, and the end-odontic opinion.

Some Opinions about the Approach to Dental CariesThe classic cariologist opinion is focused on the prevention of caries and further

progression of the established lesion. The initial focus is on the white spot lesion, whosehistologic picture is visualized in the laboratory via transmitted or polarized light.Treatment philosophies here are typically related to nonoperative and preventive ap-proaches. If caries has progressed into the dentin, with demineralized dentin beingvisible on the x-ray or, at most, extending through half the thickness of the dentin,excavation procedures are planned to avoid pulp exposures.

The operative opinion is typically initiated when caries has progressed into aclinical breakdown of the enamel surface and with carious dentin exposure. Withoutfocusing on specific details about caries pathology, the cavity needs to be “drilled andfilled.” A lesion means an exposure of the pulp, and this might be avoided by leavingcarious dentin behind. The operative opinion also tends to be a two-edged sword,because sometimes the design of the cavity overrides the fact that the caries lesion mightnot be in need of operative intervention. However, for esthetic or other reasons, theoperative intervention is carried out with a minimally invasive approach, even thoughthe actual lesion is dark, discolored, arrested caries.

Finally, the endodontic opinion deals with the prevention of an infected pulp andsubsequent apical pathosis; the issue of a lesion mainly concerns this region. Therefore,all carious dentin should be removed, even if the result is a pulp exposure. The existenceof these virtual opinions was reflected in a recent practice-based research network todetermine dentists’ treatment methods for deep caries lesions in which one wouldexpect pulpal exposure (1). The survey findings showed that 62% of the respondingdentists would remove all caries (operative opinion), 18% would partially removecaries (cariologist opinion), and 21% would initiate endodontic treatment (endodonticopinion). Differences in decision making for treating deep carious lesions in primarymolars have also recently been reported (2).

Actually, this topic is not new, as shown in the following quotations: “It is better thata layer of discolored dentin should be allowed to remain for the protection of the pulprather than run the risk of sacrificing the tooth” (3). In contrast, Black (4) wrote:“. . . it will often be a question whether or not the pulp will be exposed when all decayeddentin overlaying it is removed . . . It is better to expose the pulp of a tooth than to leaveit covered only with softened dentin.”

It is necessary to remain within the historical perspective to understand how thesedifferent opinions have justified various treatment concepts. The endodontic opinionadvocating an invasive pulp treatment in relation to caries might very well have gained

From the Department of Cariology and Endodontics,School of Dentistry, Faculty of Health Sciences, University ofCopenhagen, Denmark.

Address requests for reprints to Dr Bjørndal at [email protected].

Conflict of Interest: Lars Bjørndal, DDS, PhD, is a GrantRecipient from the Danish Agency for Science Technology andInnovation.0099-2399/$0 - see front matter

Copyright © 2008 American Academy of Pediatric Den-tistry and American Association of Endodontists.

This article is being published concurrently in PediatricDentistry, May/June 2008; Volume 30, Issue 3. The articles areidentical. Either citation can be used when citing this article.doi:10.1016/j.joen.2008.02.037

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S2 Bjørndal JOE — Volume 34, Number 7S, July 2008

inspiration from pulp studies carried out on animal models by usingstandardized test cavities in sound dentin, in which the pulp reacts veryearly to the influx of various external stimuli. These stimuli might in-clude samples of plaque or soft carious dentin (5, 6). In this context, thestudy by Brännström and Lind (7) has been a key reference, showingthat the early enamel lesion in human teeth could also lead to odonto-blast alterations and signs of pulpal infiltration. This is a key referencebecause in this symposium presentation it is hypothesized that thesefindings have been used as evidence for the early onset of irreversiblepulpal inflammation caused by caries progression. Taken together, it istempting to suggest that the observation of the “early influx pulp data”might have led to the clinical interpretation that irreversible pulp in-flammation is also reached relatively early in relation to caries. There-fore, radical interventions have been advocated. A recent Cochranereview of pulp management in extensive caries deals with clinical stud-ies in which deep lesions without clinical symptoms were treated (8).One could question why a pulp-preserving treatment was not an option.

In contrast, the cariologist opinion, and to some extent the oper-ative opinion, can be traced back decades to Massler (9). Massler,among others, integrated a sophisticated and advanced biologic under-standing of caries into caries treatment. He described acute and chroniccaries on the basis of clinical criteria and histologic descriptions. Con-sequently, different pulpal reaction patterns were to be expected thatcould lead to differing means of treating caries as opposed to only aradical approach.

With the metaphor of the caries train in mind, it is too much toforce everyone to get on and off at all the stations, but during a sympo-sium such as this, a natural goal would be to reach a consensus ofunderstanding caries in between these group opinions. Therefore, whenentering a caries discussion aiming to cross invisible lines of dentalsubspecialities, it is necessary to be clear and precise with the use ofwell-defined terms. Why? Because the interpretation of the very sameclinical situation even today might reflect completely different treat-ments (1, 2), and misunderstandings might very well occur in commu-nication between clinicians and researchers. Let us update our under-standing of caries pathology by considering that the caries train mightuse more than one track. This reflects the understanding and impor-tance of caries as a disease that can progress at varying rates.

What is the sequence of the various zones in carious dentin, be-ginning with early lesions? When and how does the pulp begin to pro-duce extradentinal matrix and tertiary dentin? What is the spreadingpattern of caries? When will microorganisms invade the demineralizeddentin? Can we say something about the prehistory of caries, whenviewing the histologic picture of tertiary dentin? Why do we sometimesfind tertiary dentin produced during caries, whereas at other times it isdifficult to detect? Is knowledge about lesion activity important?

An Update of Caries Pathology: The Non-cavitatedEnamel Lesion Complex—Understanding the Early

Pulp–Dentinal Response to CariesThe proximal white spot lesion is triangular when viewed in 2

dimensions and conical when viewed in 3 dimensions. On the basis ofquantitative data related to the degree of porosity in the enamel lesion,the lesion comprises a multitude of many microlesions following thedirection of the enamel rods. Hence, the topography of the lesion re-flects the acidogenic potential of the cariogenic biofilm at the enamelsurface. The central lesion area is the oldest part and shows the deepestpenetration, whereas the peripheral parts represent “new beginners”following the direction of the rods (10).

In short, the shape of the enamel lesion represents a transmissionof stimuli from the enamel surface that can be related to time and

provides the possibility for understanding the subjacent pulpal-dentinalresponse in relation to time. Thus, the deepest penetration of the entirecaries lesion complex can also be seen as the oldest lesion area alongthe dentin-pulp interface following the direction of the dentinal tubules.Consequently, the peripheral areas represent younger and less pro-gressed areas along the dentin-pulp interface, guided by the cariogenicbiofilm covering the surface of the enamel lesion. The morphology ofreactionary dentinogenesis, defined as tertiary dentin produced by pri-mary odontoblasts, has been described by using this concept (11). I willreturn to this subject later.

Examples of Improved Laboratory Methods That HaveCreated a Better Understanding

One approach that has improved our understanding from the his-tologic findings of Brännström and Lind (7) was the use of thin, un-demineralized tooth sections in the examination of well-defined cariouslesions. The normal structural relationships between enamel, dentin,and the pulp were preserved with this new histologic method. There-fore, it was possible to describe morphologic changes in the enamel andthe subjacent pulp-dentinal organ within the same section (12). Also,the application of immunohistochemistry has improved our under-standing of the underlying molecular events (13), as well as reactionsleading to reactionary and reparative dentinogenesis (14).

The Sequence of the Carious Development inthe Tooth

Morphologic changes in odontoblasts have been found in well-defined enamel lesions in freshly extracted third molars (14). More-over, morphologic and molecular features in the odontoblast cells lead-ing to the production of extradentinal matrix can also be detected (15,16). During our daily clinical practice we might only recall the earlyodontoblast response from the library, but when we experience the pulpin relation to caries, it is during a very late stage of lesion progression aswe consider whether pulp exposure should be avoided.

How should we interpret the early pulp response? An updatedinterpretation and understanding would be that the pulpal responsefollows the caries lesion from the very beginning. However, it should notbe considered as a “station” along the track of irreversible pulp inflam-mation, hence a “point of no return.” Some observations even indicatethat the pulp might react to the signals passing through the enamel evenbefore histologic caries reactions can be observed in the dentin (14).

The first visible histologic change in the dentin subjacent to anenamel lesion is the formation of hypermineralized dentinal tubules.This reaction is seen in the dentin before any signs of demineralization.The reaction might represent activity of the odontoblasts, and it mightvery well resemble the age-related intratubular physiologic sclerosis(17). When the enamel lesion reaches the dentinoenamel junction(DEJ), dentin demineralization is initiated. Note that the initial dentindemineralization takes place not in unaffected sound dentin but in den-tin with a decreased permeability as a result of the presence of thehypermineralized dentin.

After the dentin begins the process of demineralization, the ad-vancing front of demineralization also reflects the dynamic nature of thecariogenic biofilm, expressed as different pH gradient creating eitherdissolution or reprecipitation of dentin mineral. Thus, the hyperminer-alized dentin is probably the result of physiologic activity from the odon-toblast, but it also contains reprecipitation of previously dissolved den-tin crystals. However, this topic requires additional study (18).

No serious microbial invasion takes place in the dentin as long asthe highly organized enamel layer (even though being demineralized)separates the biofilm from the dentin. The bacteria are not able to

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JOE — Volume 34, Number 7S, July 2008 The Caries Process and Its Effect on the Pulp S3

penetrate through the enamel rod structure (19). The microbial invasion isrelated to the gradual structural breakdown of the enamel layer (20).

Another important change in our understanding is the misinter-preted concept of caries spreading along the DEJ subjacent the non-cavitated enamel lesion (21). The extent of the demineralized dentin isrestricted to the histologic enamel lesion contact, and no spreading ofdemineralized hard tissue is noted undermining sound enamel. Thelateral spread of demineralized dentin and enamel is related to the totalbreakdown of the enamel layer and therefore describes a relatively laterstage of tissue destruction than previously believed.

During the stages of dentin exposure a completely different situa-tion is created under heavy bacterial invasion. A moist, soft, disinte-grated, demineralized, and necrotic zone is observed. At this active stagethe carious dentin can easily be separated from the enamel. The outfluxof mineral has been extensive, and as the moisture is decreased, even-tually the dentin shrinks, and a clinically visible gap develops betweenthe enamel and dentin (Fig. 1a). Subsequently, the cariogenic biofilmgains improved growth conditions along the lateral spread of caries orretrograde caries (23). If the carious tooth is left untreated, furthertissue breakdown occurs. Eventually the caries process will bring aboutirreversible changes in the pulp, leading to necrosis and pulpal infectionwith apical pathosis. This worst case scenario is often what we find inmany textbooks. It also represents what takes place several times a weekin dental practice. In Denmark caries is still the most frequent reasonfor endodontic treatment (24).

Lesion Activity and Pulpal ResponseWhat is the significance of how rapidly caries progresses in rela-

tion to a pulpal response? Let us once again benefit from the histologicfindings of the early pulp response to enamel caries (14). In addition toodontoblast cell reaction per se, the odontoblasts also display a differentresponse to active versus arrested caries. When the non-cavitatedenamel lesion has histologic contact with the DEJ, the odontoblastswithin active lesions have a significantly lower cytoplasm:nucleus ratiocompared with control sites. In contrast, this situation is not found in thearrested or slowly progressing enamel lesion. Moreover, only activeenamel lesions show evidence of proliferation of cells from the sub-odontoblastic cell-rich zone into the cell-free zone. In short, the pulpalresponse follows not only the early caries lesion; it also mirrors changesin lesion activity.

In cavitated lesions, different patterns of tertiary dentin can beexpected relative to the prehistory of each lesion. The presence orabsence of tertiary dentin, as well as its quality, should be seen as areflection of the nature of the external stimuli that have previouslypassed through the dentin. As an additional example, the rapidly pro-gressing caries lesions would typically follow the sequence of odonto-

blast necrosis (25), eventually followed by the presence of atubulardentin formation, also known as fibrodentin. Let us in this contextreturn to the morphology of the reactionary dentinogenesis defined astertiary dentin produced by primary odontoblasts. A few studies havedescribed this sequence by comparing central and old lesion areas withperipheral and lateral parts of younger lesion areas (11, 14). It appearsthat the primary odontoblasts are involved in the early onset of newextradentinal matrix in the younger portions of the lesion, whereas theolder central lesion area shows the gradual development of atubularfibrodentin (26).

In contrast, slowly progressing lesions characteristically displaytubular dentin formation at the pulpal site. This tertiary dentin shows amixture of reactionary dentinogenesis and dentin produced by newodontoblast-like cells. It appears that this takes place in the same man-ner as the primary odontoblast cells, with finger-like projections butinto the reactionary dentin (16). Very little attention has been givenpreviously to the potential capacity of the primary odontoblast to be partof tertiary dentin formation.

Also within deep carious lesions (Fig. 1), large variation in lesionactivity might appear (27). As the lesion progresses, the enamel breaksdown (Fig. 1b), and at the same time the growth conditions change forthe cariogenic biofilm. The cavitated lesion transforms from a closedecosystem into an open ecosystem (Fig. 1c). Different rates of progres-sion can therefore be present within one tooth. After the enamel break-down, the occlusal part of the tooth has no heavy plaque accumulation,as the degree of protection of the biofilm has decreased. The sub-jacent dentin discloses the clinical signs of slowly progressing cariesby its brownish discoloration (Fig. 2a). In contrast, the peripheralparts are protected, and accumulations of cariogenic biomass areapparent. On the basis of these observations, pulp vitality is notnecessarily maintained, but it indicates that deep exposed dentinlesions are not unconditionally related to an irreversible pattern ofpulp pathology, as traditionally taught in textbooks advocating in-vasive pulp treatments (28). Of course, if nothing is done with thedeep lesion even though it might be temporarily arrested, eventuallythe caries activity in the peripheral parts of the lesion leads to thebreakdown of the tooth (Fig. 2b, c).

The pulpal response in lesions with a conversion of lesion activitycan be reflected by the presence of reparative dentinogenesis, defined asthe combination of fibrodentin and new tubular dentin produced by newodontoblast-like cells (29). The presence of fibrodentin or interfacedentin indicates that all primary odontoblasts have died. After thechange in caries activity, the pulp might respond with reparative dentinresembling the dentin-bridge formation after a direct pulp capping pro-cedure (16).

Figure 1. Diagrams showing the temporary conversion of the cariogenic ecosystem during untreated lesion progress. A closed lesion environment develops in relationto an occlusal lesion (a). Eventually the white demineralized and undermined enamel breaks as a result of mechanical stress, changing the environment into an openecosystem (b). Consequently, a stage of mixed lesion activity develops. In the occlusal part, classic signs of slow lesion progress are noted in terms of a darkerappearance of the demineralized dentin, whereas at the margins, optimal growth conditions for the plaque are apparent, and active lesion progress continues (c).Red zones indicate plaque. Reprinted with permission from Blackwell Munksgaard from Bjørndal L. Dentin and pulp reactions to caries and operative treatment:biological variables affecting treatment outcome. Endodontic Topics 2002;2:10 –23. (22)

Pulp Symposium


Understanding of Caries Pathology Creates theTreatment Philosophy Related to Deep Caries

In the past, the following have all been clear justification for theperformance of radical operative intervention: (1) early microbial in-vasion of carious dentin, (2) early spreading along the DEJ that under-mines sound enamel, and (3) the early onset of an irreversible pulpresponse. Even though textbooks often illustrate the worst case sce-nario, this does not mean that we should wait for it to happen! We should bemotivated to understand the lesion activity and use this information in thetreatment of caries. Instead of accepting that there is a steady progressionthrough the tooth leading toward the same results if left untreated, it mightbe more appropriate to understand that caries activity constitutes manydifferent rates of progression, each of them leading to different pulp reac-tions. Perhaps with the appropriate clinical intervention we can reduce therate of caries progression, perhaps even arresting the subjacent pulpal in-flammation. Only well-designed clinical trials will answer this question,given that we do not yet have noninvasive tools for the measurement of theseverity of the inflamed pulp. Therefore, the clinical discussion of reversibleor irreversible development of pulpitis will continue to be controversial inrelation to the actual state of pulp pathology. However, when diagnosingdeep carious lesions, we must make a choice on the basis of our knowledgeof the caries process and its effect on the pulp and on the basis of existingdiagnostic methods. The noninvasive pulp treatment of deep caries lesionswill be the focus of my second presentation.

References1. Oen KT, Thompson VP, Vena D, et al. Attitudes and expectations of treating deep

caries: a PEARL network survey. Gen Dent 2007;55:197–203.2. Qudeimat MA, Al-Saiegh FA, AL-Omari Q, Omar R. Restorative decisions for deep

proximal carious lesions in primary molars. Eur Arch Paediatr Dent 2007; 8:37– 42.3. Tomes J. A system of dental surgery. London: John Churchill, 1859:336.4. Black GV. A work on operative dentistry in two volumes, vol. II. The technical pro-

cedures in filling teeth. 2nd ed. Chicago: Medico-Dental Publishing Co, 1908.5. Bergenholtz G, Lindhe J. Effect of soluble plaque factors on inflammatory reactions in

the dental pulp. Scand J Dent Res 1975;83:153– 8.6. Mjör IA, Tronstad L. Experimentally induced pulpitis. Oral Surg 1972;34:102– 8.7. Brännström M, Lind PO. Pulpal response to early caries. J Dent Res 1965;44:1045–50.8. Nadin G, Goel BR, Yeung CA, Glenny AM. Pulp treatment for extensive decay in

primary teeth. Cochrane Database Syst Rev 2003;1:CD003220.9. Massler M. Pulpal reactions to dental caries. Int Dent J 1967;17:441– 60.

10. Bjørndal L, Thylstrup A: A structural analysis of approximal enamel caries lesions andsubjacent dentin reactions. Eur J Oral Sci 1995;103:25–31.

11. Lee Y-L, Liu J, Clarkson BH, Lin C-P, Godovikova V, Ritchie HH. Dentin-pulp complexresponses to carious lesions. Caries Res 2006;40:256 – 64.

12. Bjørndal L, Thylstrup A, Ekstrand KR. A method for light microscopy examination ofcellular and structural interrelations in undemineralized tooth specimens. Acta Od-ontol Scand 1994;52:182–90.

13. Yoshiba N, Yoshiba K, Nakamura H, Iwaka M, Ozawa H. Immunohistochemical lo-calization of HLA-DR-positive cells in unerupted and erupted normal and carioushuman teeth. J Dent Res 1996;75:1585–9.

14. Bjørndal L, Darvann T, Thylstrup A. A quantitative light microscopic study of odon-toblast and subodontoblastic reactions to active and arrested enamel caries withoutcavitation. Caries Res 1998;32:59 – 69.

15. Lukinmaa PL, Vaahtokari A, Vainio S, Thesleff I. Expression of type I collagen pro-�2

chain mRNA in Adult human permanent teeth as revealed by in situ hybridization. JDent Res 1992;71:36 – 42.

16. Bjørndal L, Darvann T. A light microscopic study of odontoblastic and non-odonto-blastic cells involved in tertiary dentinogenesis in well-defined cavitated cariouslesions. Caries Res 1999;33:50 – 60.

17. Tagami J, Hosoda H, Burrow MF, Nakajima M. Effect of ageing and caries in dentinpermeability. Proc Finn Dent Soc 1992;88(Suppl 1):149 –54.

18. Kidd EAM, Bjørndal L, Beighton D, Fejerskov O. Caries removal and the pulpo-dentinal complex. In: Fejerskov O, Kidd EAM, eds. Dental caries: the disease and itsclinical management. 2nd ed. Oxford: Blackwell Munksgaard, 2008:367– 83.

19. Ekstrand KR, Bjørndal L. Structural analyses of plaque and caries in relation to themorphology of the groove-fossa system on erupting mandibular third molars. CariesRes 1997;31:336 – 48.

20. Ricketts D, Ekstrand KR, Kidd EAM, Larsen T. Relating visual and radiographicranked scoring systems for occlusal caries detection to histological and microbio-logical evidence. Oper Dent 2002;27:231–7.

21. Silverstone LM, Hicks MJ. The structure and ultrastructure of the carious lesion inhuman dentin. Gerodontics 1985;1:185–93.

22. Bjørndal L. Dentin and pulp reactions to caries and operative treatment: biologicalvariables affecting treatment outcome. Endodontic Topics 2002;2:10 –23.

23. Bjørndal L, Kidd EAM, The treatment of deep dentine carious lesions. Dent Update2005;32:402–13.

24. Bjørndal L, Laustsen MH, Reit C. Root canal treatment in Denmark is most oftencarried out in carious vital molar teeth and retreatments are rare. Int Endod J2006;39:785–90.

25. Magloire H, Bouvier M, Joffre A. Odontoblast response under carious lesions. ProcFinn Dent Soc 1992;88(Suppl.1):257–74.

26. Bjørndal L. Presence or absence of tertiary dentinogenesis in relation to cariesprogression. Adv Dent Res 2001;33: 80 –3.

27. Edwardsson S. Bacteriology of dentin caries. In: Thylstrup A, Leach SA, Qvist V, eds.Dentine and dentine reactions in the oral cavity. Oxford: IRL Press, 1987:95–102.

28. Tronstad L. Clinical endodontics. 2nd ed. Stuttgard: Thieme, 2003:81.29. Smith AJ, Tobias RS, Cassidy N, et al. Odontoblast stimulation in ferrets by dentine

matrix components. Arch Oral Biol 1994;39:13–22.

Figure 2. The pattern of untreated deep lesions might involve a decrease in lesion activity (a), but it might be temporary because the enamel margins will obtainprotection for the cariogenic process (b). Eventually the entire crown breaks, leaving remnants of roots behind (c). Red zones indicate plaque. Reprinted withpermission from Blackwell Munksgaard from Bjørndal L. Dentin and pulp reactions to caries and operative treatment: biological variables affecting treatmentoutcome. Endodontic Topics 2002;2:10 –23. (22)

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JOE — Volume 34, Number 7S, July 2008 The Caries Process and Its Effect on the Pulp S5

Diagnosis Dilemmas in Vital Pulp Therapy: Treatment forthe Toothache Is Changing, Especially in Young,Immature TeethJoe H. Camp, DDS, MSD

AbstractThe literature is almost devoid of scientific studies ofdiagnosis of pulpal pathology in primary and perma-nent teeth with open apices. Most reports are empiricalor retrospective studies without adequate prior knowl-edge of preexisting conditions or histologic findingsleading to the necessity of pulpal procedures. Appro-priate diagnostic tests and their effectiveness are doc-umented for both groups. This article reviews the avail-able literature and current techniques of indirect pulptherapy, pulp capping, and pulpotomy for primary teethand permanent teeth with open apex. The apical bar-rier with mineral trioxide aggregate followed by rootstrengthening with bonded composite is reviewed.(J Endod 2008;34:S6-S12)

Key WordsDiagnosis, pulp, pulp capping, pulpotomy

Diagnosis in primary and young, permanent, immature teeth varies greatly from thatin fully formed permanent teeth. Most of the diagnostic tests used in conventional

endodontic therapy are of very little or no value in primary teeth and of limited value inpermanent immature teeth. While admittedly poor for diagnosing the degree of inflam-mation in this group of teeth, diagnostic tests must be performed to obtain as muchinformation as possible before arriving at treatment options.

Diagnostic literature based on scientific studies is almost nonexistent. Most out-come reports are supported by empirical treatment and anecdotal case reports (1).Many outcome studies are conducted retrospectively on the basis of clinical signs andsymptoms and make assumptions regarding the pulpal status before treatment withouthistologic or bacterial data to support the preoperative diagnosis. Without histologicexamination an accurate determination of the extent of inflammation is impossible (2).Correlation between clinical symptoms and histopathologic conditions is poor andcomplicates diagnosis of pulpal health in exposed pulps of children (3).

Many of our treatments are based on our diagnosis of the root development stage.Consequently, to properly diagnose and treat primary and young permanent teeth, it isnecessary to have a thorough knowledge of normal root formation and the differencesbetween developing and fully formed teeth. The decision to render conservative vitaltreatment to allow root formation completion or more radical treatment such as rootcanal therapy might hinge on our diagnosis of root development.

According to Orban (4), the tooth root’s development begins after enamel anddentin formation has reached the cementoenamel junction (CEJ). Hertwig’s epithelialroot sheath is formed by the epithelial dental organ, with one tube for each of the futureroots. As root formation proceeds apically, each root is wide open, diverging apicallyand limited by the epithelial diaphragm. Each root’s internal surface is lined by odon-toblasts. Once root length is established, the sheath disappears, whereas dentin depo-sition is continued until root formation is completed.

Depending on each root’s external anatomy, differentiation into multiple canalsmight occur. During this formative stage, communication exists between the canals inthe form of isthmuses. As growth continues, the opposing walls meet and coalesce, andislands of dentin are formed, which eventually expand to divide the root into separatecanals. Continued dentin deposition narrows the canals, and the apex is eventuallyclosed with dentin and cementum, creating apical convergence. Isthmuses and finsextending toward the root’s center might persist in fully formed teeth.

In permanent teeth, root formation is not completed until 1– 4 years after eruptioninto the oral cavity. Because of the shorter roots of primary teeth, root formation iscompleted faster than for permanent teeth. Because the faciolingual width of most rootsand canals is greater than the mesiodistal width, apical closure cannot usually bedetermined radiographically. The x-ray beam is exposed in the faciolingual plane, butthe radiograph is read mesiodistally. Because of this anatomy, with the exception of themaxillary central and lateral incisors and some single canal lower premolars, radio-graphs cannot determine apical closure. Therefore, the clinician must rely on time todetermine root closure in all other teeth to prevent treatment protocols that cannot besuccessfully completed without apical convergence (5).

During this formative period, treatments should be oriented toward maintenanceof vitality to allow completion of root formation. Further deposition of dentin willstrengthen the roots’ thin dentinal walls and help diminish future root fracture.

From private practice of endodontics, Charlotte, NorthCarolina, and Department of Endodontics, University of NorthCarolina, Chapel Hill, North Carolina.

Address requests for reprints to Dr Camp at E-mail address:[email protected].

Conflict of Interest: Joe H. Camp, DDS, MSD, is the Uni-versity Clinical Consultant for Dentsply Tulsa Dental Special-ties, a part-time, paid position.0099-2399/$0 - see front matter



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The root canals of primary teeth differ greatly from those of per-manent teeth, and treatment is complicated by apical resorption toallow for eruption of the succeeding teeth. At the time of root lengthcompletion, the root canals roughly correspond to the externalanatomy’s form and shape. At this time, resorption of the rootsbegins and, combined with additional dentin deposition internally,might significantly change the number, size, and shape of the canalswithin the primary roots. Continued physiologic, apical resorption ofthe roots makes the teeth progressively shorter. In addition, resorptionon the roots’ internal surfaces adjacent to the forming permanent toothmight open other communications with the periapical tissues. Thesefactors complicate establishment of working lengths if root canal ther-apy is necessary.

In the primary anterior teeth (incisors and canines), the perma-nent tooth buds lie apically and lingually near the primary roots. Re-sorption is initiated on the primary root’s lingual surface. This causesthe apical foramen to move coronally, resulting in a difference in theapical foramen and the anatomic apex and complicating determinationof root canal length. One study demonstrated that half of the primaryincisor’s root might be resorbed lingually before it becomes obvious ona radiograph (6). Primary anterior teeth have one simple root canal andrarely have lateral or accessory canals.

The primary molar teeth normally have the same number andposition of roots and root canals as the corresponding permanent teeth.At root length completion, most roots have only 1 canal, but continueddeposition of dentin might divide the root into 2 or more canals (7–9).During this time, communication exists between the canals in the formof isthmuses or fins (Fig. 1). Secondary dentin deposition contributes tothis change in morphology (10, 11). Like the permanent molars, mostvariations occur in the mesial roots of mandibular molars and facialroots of the maxillary molars. Also, these variations are usually in thefacial to lingual plane and cannot be visualized on radiographs (7, 9).

Accessory and lateral canals and apical ramifications of the pulpare common in primary molars (8). In addition, other communicationsbetween the pulp and the periapical tissues are formed by physiologicresorption of the internal surfaces of the roots adjacent to the perma-nent tooth buds.

Diagnosis of Pulpal Status in Primary TeethAs with any dental procedure, a thorough medical history must be

completed, and any implications related to treatment must be consid-

ered. A child with systemic disease might necessitate different treatmentthan a healthy one.

The examination should begin with a thorough history and char-acteristics of any pain, because these are often important in helping todetermine pulpal status and eventual treatment. Whereas pain usuallyaccompanies pulpal inflammation, extensive problems might arisewithout any history of pain. If possible, a distinction between provokedand spontaneous pain should be ascertained. Provoked pain that ceasesafter removal of the causative stimulation is usually reversible and in-dicative of minor inflammatory changes. Stimuli include thermal, chem-ical, and mechanical irritants and many times are due to deep caries,faulty restorations, soreness around a primary tooth nearing exfoliation,or an erupting permanent tooth.

Spontaneous pain is a constant or throbbing pain that occurs with-out stimulation or continues long after the causative factor has beenremoved. In a well-controlled histologic study of primary teeth withdeep carious lesions, Guthrie et al. (12) demonstrated that a history ofspontaneous toothache is usually associated with extensive degenerativechanges extending into the root canals. Primary teeth with a history ofspontaneous pain should not receive vital pulpal treatments and arecandidates for pulpectomy or extraction.

The clinical examination might produce evidence of pulpal patho-sis. Redness, swelling, fluctuance, severe dental decay, defective ormissing restorations, and draining parulis might indicate pulpal involve-ment. Percussion sensitivity might be valuable to the diagnosis, but it iscomplicated by the reliability of the child’s response because of thepsychological aspects involved. Tooth mobility might be present nor-mally because of physiologic resorption, and many pulpally involvedteeth have no mobility.

Electric pulp tests are not valid in primary teeth (1). Laser Dopplerflowmetry might be of greater help in determining vitality, but this equip-ment has not been perfected, and the price is prohibitive (13).

Thermal tests are usually not conducted on primary teeth becauseof their unreliability (1, 5).

After the clinical examination, radiographs of good quality areessential. Like permanent teeth, periapical radiolucencies appear at theapices in primary anterior teeth. In primary molars, pathologic changesare most often apparent in the bifurcation or trifurcation areas. Conse-quently, bite-wing radiographs are often best to observe pathologicchanges in posterior primary teeth. Pathologic bone and root resorp-tions are signs of advanced pulpal pathosis that has spread into theperiapical tissues and is usually treatable only with extraction.

Mild, chronic pulpal irritation such as seen in caries might stim-ulate the deposition of tertiary reactionary dentin over the pulp (5).With acute or rapid onset as the disease reaches the pulp, calcifiedmasses might form away from the exposure site. Such calcified massesare always indicative of advanced pulpal degeneration extending intothe root canals (14). Primary teeth with such calcified masses arecandidates for only pulpectomy or extraction (Fig. 2).

Internal resorption in primary teeth is always associated with ex-tensive inflammation (12). Because of the thinness of the primary molarroots, if internal resorption can be seen radiographically, a perforationusually exists, and the tooth must be extracted (Fig. 3).

Interpretation of radiographs of primary teeth is always compli-cated by the presence of the succedaneous tooth and surrounding fol-licle. Misinterpretation of the follicle can easily lead to an erroneousdiagnosis of periapical pathology. Superimposition of the permanenttooth might obscure visibility of the furca and roots of the primary tooth,causing misdiagnosis. Added to this is the normal physiologic resorp-tion process.

Radiographs might also reveal evidence of: previous pulpal treat-ment; calcification changes in pulp chambers and root canals; oversized

Figure 1. Silicone models of the pulps of 2 primary mandibular second molars.Note the communication between the facial and lingual canals in the mesialroots.

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JOE — Volume 34, Number 7S, July 2008 Diagnosis Dilemmas in Vital Pulp Therapy S7

canals indicative of cessation of root formation and pulpal necrosis; andafter trauma, root fractures, bone fractures, displacement of teeth, im-bedded tooth fragments, or foreign bodies in soft tissues.

The size of a pulpal exposure and the amount and color of hem-orrhage have been reported as important factors in diagnosing theextent of inflammation under a carious lesion. Although all cariousexposures are accompanied by pulpal inflammation, the larger the ex-posure, the more likely it is to be widespread or necrotic.

Excessive (2, 5, 14, 15) or deep purple (15) colored hemorrhageis evidence of extensive inflammation, and these teeth are candidates forpulpectomy or extraction. Hemorrhage that cannot be controlled within1–2 minutes by light pressure with a damp cotton pellet at an exposuresite indicates more extensive treatment is necessary. The same is trueafter removal of tissue when doing a pulpotomy. A pulpectomy or ex-traction would then be indicated.

In addition to the aforementioned tests and observations whendealing with traumatic injuries to the primary teeth, other factors mustbe considered.

Studies have shown that 1 in 3 children receive traumatic injuriesto the primary dentition (16, 17). Because of the less dense bone andshorter roots as compared with permanent teeth, most injuries aredisplacements rather than fractures. Such injuries might heal normallywithout sequelae by formation of an amorphous diffuse calcificationhistologically resembling osteodentin, formation of a partial or com-plete obliteration of the canal (18, 19), or result in pulpal necrosis.

In a study of 545 traumatized primary maxillary incisors, Borumand Andreasen (20) found that 53% of subjects developed pulpal ne-crosis, and 25% developed pulp canal obliteration. The factors found toinfluence development of pulp necrosis were age of the patient, degreeof displacement and loosening, and concurrent crown fracture. Calcificobliteration of the canal was influenced by tooth displacement andamount of root resorption. Crown fracture decreased canal oblitera-tion. They also pointed out that no well-established treatment guidelinesexist concerning healing processes and complications in primary teeth.

It has been suggested that the proximity to the succedaneous toothis an important factor when deciding on treatment for the injured pri-mary tooth. The treatment least likely to damage the permanent toothshould be chosen (1, 20). Conflicting data exist regarding treatment ofprimary injuries. Studies have shown no relationship between treatinginjured primary teeth compared with extraction regarding disturbanceof the permanent teeth (16, 21). Others have shown a tendency towardmore extensive disturbances in the mineralization when injured pri-mary teeth were retained (22).

Near universal agreement exists that avulsed primary incisorsshould not be replanted because of the possibility of danger to thepermanent tooth bud (1).

Roughly half of traumatized primary teeth presenting for treatmentdevelop transient or permanent discoloration. These colors vary fromyellow to dark gray and usually become evident 1–3 weeks after trauma.Primary teeth with yellow discoloration frequently have radiographicsigns of pulp canal calcification and have a low incidence of pulpalnecrosis (20, 23).

Injured primary teeth with dark gray discoloration are reported tohave necrotic pulps in 50%– 82% of the cases. Conversely, necrosis ofthe pulp occurred in teeth with no discoloration in approximately 25%of injured primary incisors (20, 23–25). Attempts to correlate discol-oration to pathologic, radiographic, and histologic changes in the pulpsof injured primary incisors present mixed findings. Color change of thetooth alone without other findings is not a reliable indicator of pulpalhealth (26). Diagnosis of pulp necrosis in primary incisors is primarilybased on dark gray color change and radiographic evidence of peria-pical pathology or lack of root formation (1) (Fig. 4). Schroder et al.(25) reported development of periapical osteitis in 82% of gray discol-orations within 1 month. Andreasen and Riis (27) have shown that pulpnecrosis and periapical inflammation of 6 weeks’ duration did not leadto developmental disturbances of permanent teeth. Thus, when diagno-sis cannot be established, it is justifiable to wait for further develop-ments.

Diagnosis of Pulpal Status in PermanentImmature Teeth

In teeth with incomplete root formation, correct pulpal and peri-apical diagnosis is of paramount importance before proceeding withany endodontic treatment because of the devastating result of loss ofvitality. Every attempt should be made to preserve the vitality of theseimmature teeth until maturation has occurred. Loss of pulpal vitalitybefore completion of dentin deposition leaves a weak root more proneto fracture as a result of the thin dentinal walls.

In a 4-year study, Cvek (28) noted a significant increase in cervicalroot fractures in treated immature teeth compared with those with com-pleted roots. In immature teeth, the frequency of fractures was depen-dent on the stage of root development, ranging from 77% in teeth withthe least to 28% in teeth with the most developed roots (28). Thus, evenif treatment is successful, prognosis for prolonged retention of the tooth

Figure 2. Calcified masses within the pulp (arrow), which form away from theexposure site, and internal resorption (as in this primary mandibular firstmolar) are indicative of advanced degeneration.

Figure 3. Internal resorption (arrow), as seen in this primary maxillary secondmolar, will always be perforated and a candidate for extraction. Note the per-forated root after extraction and the periodontal probe in the resorptiveperforation.

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is greatly diminished. Loss of vitality before completion of root lengthwill lead to a poorer crown-to-root ratio, with possible periodontalbreakdown as a result of increased mobility. Therefore, all treatments inthis group of teeth are oriented toward vital procedures. If these moreconservative procedures fail, the tooth can still be treated with apexifi-cation, apical barrier techniques, or conventional root canal treatment.

Although numerous scientific studies have been reported on thetreatment of permanent teeth with immature apices, the literature isalmost devoid in the area of diagnosis of pulpal status in this group ofteeth.

The diagnosis begins with a thorough medical history and anyimplications related to the anticipated treatment. The dental history andcharacteristics of associated pain might be helpful in determining pul-pal status. History of any traumatic injury to the facial area should beexplored in depth and recorded for future medical, dental, legal, andinsurance purposes.

The nature, type, length, and distinction between provoked andspontaneous pain are recorded. Provoked pain caused by thermal,chemical, or mechanical irritants usually indicates pulpal inflammationof a lesser degree and is often reversible. Spontaneous pain, on theother hand, is usually associated with widespread, extensive, degener-ative, irreversible pulpal inflammation or necrosis.

The medical and dental histories are followed by a thorough clin-ical examination. Any areas of redness, swelling, fluctuance, tissue ten-derness, dental decay, defective or missing restorations, or fractured ormobile teeth are noted. Presence of discolored crowns or a parulismight indicate pulpal necrosis. The alignment of the teeth, including anyinfrapositioned or suprapositioned teeth, might provide valuable infor-mation.

Electric pulp tests and thermal tests are of limited value because ofthe varied responses as roots mature. In addition, invalid data mightbe obtained as a result of the often unreliable responses from chil-dren because of fear, management problems, and inability to un-

derstand or communicate accurately. Consequently, most diagnosesare made on observation of clinical symptoms and radiographicevidence of pathosis.

Numerous studies (29 –32) have reported the unreliability of elec-tric pulp tests in permanent teeth with open and developing apices.Inconsistent results ranging from 11% in 6- to 11-year-olds with com-pletely open apices (29) to 79% in older children (31) have beenreported. It is also possible to obtain a false-positive in teeth with liq-uefaction necrosis (33). Thus, electric pulp tests are of little valueduring the period of root formation, because the data are not reliable.

Electric and thermal tests were shown to be unreliable aftertraumatic injury to a tooth, and no response might be elicited evenafter circulation has been restored (34, 35). The potential for heal-ing is greater with incomplete root development than in fully formedteeth.

Laser Doppler flowmetry has been reported to be very reliable fordiagnosing pulpal vitality (13, 36, 37). In a very detailed histologic andradiographic study of revitalization of dogs’ teeth after reimplantation,Yanpiset et al. (36) were able to make a correct diagnosis 84% of thetime. In nonvital pulps, the histologic study proved to be accurate in95% of cases, whereas in vital ones the data were correct 74% of thetime. This significant difference in readings was observed at as earlyas 4 weeks. Although the authors pointed out the validity of deter-mining nonvital teeth, they cautioned against relying solely on thistest and would only initiate pulpal therapy after observing othersigns of pathology.

It has also been shown that blood pigment within a discoloredtooth crown interferes with laser light transmission (38). This limitationis significant, because discoloration after trauma is frequent. Also, thisequipment has not been perfected for routine dental diagnosis and iscost-prohibitive for the practicing dentist.

Thermal testing with ice and ethyl chloride are of limited valuediagnostically. Ice and ethyl chloride have consistently been reported tobe inferior to carbon dioxide snow (29 –32) and dichlorodiflu-oromethane (DDM) (31, 39). Researchers have shown carbon dioxidesnow to consistently give positive responses near 100% even with openapices (29 –32).

Figure 4. The dark gray discoloration of the crown of this primary maxillarycentral incisor is indicative of pulpal necrosis.

Figure 5. Dark gray discoloration of the crown of this permanent maxillarycentral incisor indicates pulpal necrosis.

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Thermal tests with heat in permanent teeth with developing apicesare of limited value because of inconsistent responses (32) and arerarely performed.

Radiographic examination and interpretation are key elements in thediagnosis of pulpal pathology in teeth with developing apices. Good qualityperiapical radiographs of any involved teeth are used to assess root devel-

opment and discover periapical rarefaction and root resorption. After trau-matic injury, radiographs are essential to determine the presence of frac-tured bone and roots, displaced teeth, and imbedded foreign objects.

In posterior teeth, bite-wing radiographs are also necessary todetect caries, proximity of lesions to the pulp, previous pulpal treat-ments, and quality of any restorations.

Figure 6. Apical barrier with MTA and strengthening of the thin root with bonded composite. (A) Preoperative radiograph of permanent maxillary left central incisor.The pulp is necrotic, and the apex is open. (B) 4-mm plug of MTA placed at the apex. (C) Remainder of canal restored with bonded composite resin.(D) Two-and-a-half–year follow-up showing covering of MTA with cementum and healing of a periapical lesion.

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Discoloration of a tooth crown after trauma is a common sequelaand one of the foremost diagnostic indicators (40 – 42). Yellow discol-oration is usually indicative of pulp space calcification, and a gray colorusually signifies pulpal necrosis (40) (Fig. 5).

Transient coronal discoloration has been reported (42) in 4% ofteeth after luxation injuries as a result of vascular damage and hemor-rhage immediately after injury. In these cases, it was speculated thatpulpal healing depends on the bacterial status. With bacterial infection,healing is unlikely. In this group of teeth, determination of bacterialstatus could not be ascertained on the basis of coronal discoloration,loss of pulpal sensibility, or periapical rarefaction (42).

Transient apical breakdown occurs after displacement injuriesand might lead to misdiagnosis (42, 43). The development of transientperiapical radiolucency—together with coronal discoloration, negativeelectric pulp test, and cold response up to 4 months—was shown tosubsequently regain the original color and normal pulpal responses(43). Transient apical breakdown apparently is linked to the repairprocess in the pulp and periapical tissues and returns to normal whenhealing is complete (42). Bone loss, which produces the radiolucency,eventually heals with new bone.

Universal agreement exists that immature teeth have the greatestpotential to heal after trauma or caries, particularly when the apicalforamen is wide open. This group of teeth also has the greatest chanceof misdiagnosis and mistreatment. To avoid mistakes, treatment mustnot be undertaken on the basis of negative responses to pulp testing.Radiographic and symptomatic assessment is currently the principaldiagnostic criterion. The following factors are key in making the diag-nostic determination: symptoms of irreversible pulpitis or apical peri-odontitis; clinical signs of periradicular infection including swelling,tenderness to percussion, mobility, or parulis formation; radiographi-cally detectible bone loss; progressive root resorption; and arrestedroot development compared with other adjacent teeth (44).

If doubtful, do not start treatment. Keep the patient under closeobservation and continue to reassess the diagnostic criteria until a de-finitive diagnosis can be established.

The treatment of primary and young permanent teeth has changeddramatically in recent years as new materials have been developed andresearched. The use of calcium hydroxide (for decades the standard forpulp protection), pulp capping, and pulpotomy procedures in perma-nent teeth is being replaced with composite resins (45, 46) and mineraltrioxide aggregate (MTA) (ProRoot; Dentsply Tulsa Dental, Tulsa, OK).Pulp capping with resin composites in monkeys produced the lowestincidence of bacterial microleakage, pulpal inflammation, and inci-dence of pulpal necrosis when compared with calcium hydroxide andglass ionomer cement (46).

When compared with calcium hydroxide, MTA produced signifi-cantly more dentinal bridging in a shorter time with significantly lessinflammation and less pulpal necrosis (47– 49). MTA has been shownto be cementoconductive, with attachment of cementoblasts to the ma-terial (49). Sarkar et al. (50) studied the interactions of MTA, a syn-thetic tissue fluid, and dentin of extracted teeth. They concluded thatcalcium from the MTA reacted with phosphate in tissue fluid, producinghydroxyapatite. The sealing ability, biocompatibility, and dentinogenicactivity of the material occur because of these physiochemical reactions.

Once considered taboo, vital pulpal treatment of symptomatic per-manent teeth with MTA has been reported (5, 51, 52) to be successful,allowing continued root development. Stronger roots with greatly im-proved prognosis for permanent retention are now possible.

Loss of pulpal vitality in open apex teeth in the past led to pro-tracted treatment and often ended in early tooth loss caused by fractureof weak roots. Apical barrier techniques with MTA now allow timelycompletion of apexification and have eliminated the use of calcium

hydroxide, except as a temporary canal disinfectant. The use of MTA asan apical barrier has become the standard for treatment of the openapex pulpless tooth (Fig. 6). The development of bonded compositetechniques now allows strengthening of these weak roots to levels ofintact, fully formed roots and has virtually ended root fractures (53–56)(Fig. 6C).

Revascularization of teeth with necrotic infected canals has beenreported by using combinations of antibiotics (57, 58). The canals areaccessed and disinfected with copious irrigation of sodium hypochlo-rite. The canals are not instrumented. A paste of metronidazole, cipro-floxacin, and minocycline is placed in the canals and left for 1 month.The tooth is re-entered, and endodontic files are inserted through theapices to stimulate bleeding to produce a blood clot at the level of theCEJ. After clotting, MTA is placed over the blood clot, and a permanentexternal seal is placed. The clot is then revascularized, producing thick-ening of the canal walls and apical closure.

Stem cell research holds great hope for the future, with the aim ofhealing impaired dental tissues including dentin, pulp, cementum, andperiodontal tissues. By stimulating the body’s intrinsic capacities, wewill be able to regenerate tissues, allowing further development of teethand bone or possibly the formation of new teeth to replace those rav-aged by decay or lost to traumatic injuries.

References1. Flores MT, Holan G, Borum M, Andreasen JO. Injuries to the primary dentition. In:

Andreasen JO, Andreasen F, Andersson L, eds. Textbook and color atlas of traumaticinjuries to the teeth. 4th ed. Oxford, UK: Blackwell Munksgaard, 2007.

2. Starkey PE. Management of deep caries of pulpally involved teeth in children. In:Goldman HM, Forrest SP, Byrd DL, et al, eds. Current therapy in dentistry. vol 3. StLouis, MO: Mosby, 1968.

3. Mass E, Zilberman U, Fuks AB. Partial pulpotomy: another treatment option forcariously exposed permanent molars. J Dent Child 1995;62:342–5.

4. Orban BJ, ed. Oral histology and embryology. 4th ed. St Louis, MO: CV Mosby Co,1957.

5. Camp JH, Fuks AB. Pediatric endodontics: endodontic treatment for the primary andyoung, permanent dentition. In: Cohen S, Hargreaves K, eds: Pathways of the pulp. 9thed. St Louis, MO: Mosby, 2006:822– 82.

6. Kamijo Y. Studies on morphological change in the alveolar region of the jaw bonewith development of the permanent tooth from the standpoint of clinical anatomy.Bull Tokyo Dent Coll 1967;8:41.

7. Zurcher E. The anatomy of the root canals of the teeth of the deciduous dentition andof the first permanent molars. New York: William Wood & Co, 1925.

8. Hibbard E, Ireland RL. Morphology of the root canals of the primary molar teeth.J Dent Child 1957;24:250.

9. Finn SB. Morphology of the primary teeth. In: Finn SB, Caldwell RC, Cheraskin E,et al, eds. Clinical pedodontics. 3rd ed. Philadelphia: WB Saunders, 1967.

10. Ireland RL. Secondary dentin formation in deciduous teeth. J Am Dent Assoc1941;28:1626.

11. Bevelander G, Benzer D. Morphology and incidence in secondary dentin in humanteeth. J Am Dent Assoc 1943;30:1079.

12. Guthrie TJ, McDonald RE, Mitchell DF. Dental hemogram. J Dent Res 1965;44:678 – 82.

13. Evans D, Reid J, Strang R, Stirrups D. A comparison of laser Doppler flowmetry withother methods of assessing the vitality of traumatized anterior teeth. Endod DentTraumatol 1999;15:284 –90.

14. McDonald RE, Avery DR. Treatment of deep caries, vital pulp exposure, and pulplessteeth in children. In: McDonald RE, Avery DR, eds. Dentistry for the child and ado-lescent. 7th ed. St Louis, MO: Mosby, 1999.

15. Pinkham JR. Diagnosis. In: Pinkham JR, ed. Pediatric dentistry: infancy throughadolescence. Philadelphia: WB Saunders, 1988.

16. Andreasen JO, Ravn JJ. Epidemiology of traumatic dental injuries to primary andpermanent teeth in a Danish population sample. Int J Oral Surg 1972;1:235–9.

17. Glendor U. On dental trauma in children and adolescents: incidence, risk, treatment,time, and cost. Swed Dent J 2000;140(Suppl):1–52.

18. Robertson A, Lundgren T, Andreasen JO, Dietz W, Hoyer I, Noren JG. Pulp calcifica-tions in traumatized primary incisors: a morphologic and inductive analysis study.Eur J Oral Sci 1997;105:196 –206.

19. Holan G. Tube like mineralizations in the dental pulp of traumatized primary incisors.Endod Dent Traumatol 1998;14:279 – 84.

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20. Borum MK, Andreasen JO. Sequelae of trauma to primary maxillary incisors:I— complications in the primary dentition. Endod Dent Traumatol 1998;14:31– 44.

21. Andreasen JO, Ravn JJ. The effect of traumatic injuries to primary teeth on theirpermanent successors: II—a clinical and radiographic follow-up study of 213 teeth.Scand J Dent Res 1971;79:284 –94.

22. Selliseth N. The significance of traumatized primary incisors on the development anderuption of permanent teeth. Eur Orthodont Soc Trans 1970;46:443.

23. Holan G, Fuks AB. The diagnosis value of coronal dark-gray discoloration in primaryteeth following traumatic injuries. Pediatr Dent 1996;18:224 –7.

24. Holan G. Development of clinical and radiographic signs associated with dark dis-colored primary incisors following traumatic injuries: a prospective controlled study.Dent Traumatol 2004;20:276 – 87.

25. Schröder U, Wennberg E, Granath LE, Moller H. Traumatized primary incisors: fol-low-up program based on frequency of periapical osteitis related to tooth color. SwedDent J 1977;1:95– 8.

26. Croll TP, Pascon EA, Langeland K. Traumatically injured primary incisors: a clinicaland histological study. J Dent Child 1987;54:401–22.

27. Andreasen JO, Riis I. Influence of pulp necrosis and periapical inflammation ofprimary teeth and their permanent successors: combined macroscopic and histo-logical study in monkeys. Int J Oral Surg 1978;7:178 – 87.

28. Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hy-droxide and filled with gutta-percha: a retrospective clinical study. Endod Dent Trau-matol 1992;8:45–55.

29. Klein H. Pulp responses to electric pulp stimulator in the developing permanentanterior dentition. J Dent Child 1978;45:199 –202.

30. Fulling HJ, Andreasen JO. Influence of maturation status and tooth type of permanentteeth upon electrometric and thermal pulp testing procedures. Scand J Dent Res1976;84:286 –90.

31. Fuss Z, Trowbridge H, Bender IB, Rickoff B. Assessment of reliability of electrical andthermal pulp testing agents. J Endod 1986;12:301–5.

32. Fulling HJ, Andreasen JO. Influence of splints and temporary crowns upon electricand thermal pulp-testing procedures. Scand J Dent Res 1976;84:291– 6.

33. Ehrmann EH. Pulp testers and pulp testing with particular reference to the use of dryice. Aust Dent J 1977;22:272–9.

34. Ohman A. Healing and sensitivity to pain in young replanted human teeth: an exper-imental clinical and histologic study. Odontol Tidskr 1965;73:166 –227.

35. Bhaskar SN, Rappaport HM. Dental vitality tests and pulp status. J Am Dent Assoc1973;86:409 –11.

36. Yanpiset K, Vongsavan N, Sigurdsson A, Trope M. Efficacy of laser Doppler flowmetryfor the diagnosis of revascularization of reimplanted immature dog teeth. Dent Trau-matol 2001;17:63–70.

37. Sigurdsson A. Pulpal diagnosis. Endod Top 2003;5:12–25.38. Heithersay GS, Hirsch RS. Tooth discoloration and resolution following a luxation

injury: Significance of blood pigment in dentin to laser Doppler flowmetry readings.Quintessence Int 1993;24:669 –76.

39. Karibe H, Ohide Y, Kohno H, et al. Study on thermal pulp testing of immature per-manent teeth. Shigaku Odontol 1989;77:1006 –13.

40. Bakland LK. Endodontic considerations in dental trauma. In: Ingle JI, BaklandLK, eds. Endodontics. 5th ed. Hamilton, Ontario, Canada: BC Decker Inc, 2002:795– 843.

41. Jacobsen I. Criteria for diagnosis of pulpal necrosis in traumatized permanent inci-sors. Scand J Dent Res 1980;88:306 –12.

42. Andreasen F. Transient apical breakdown and its relation to color and sensibilitychanges. Endod Dent Traumatol 1986;2:9 –19.

43. Cohenca N, Karni S, Rotstein I. Transient apical breakdown following tooth luxation.Dent Traumatol 2003;19:289 –91.

44. Mackie IC, Hill FJ. A clinical guide to the endodontic treatment of nonvital immaturepermanent teeth. Br Dent J 1999;186:54 – 8.

45. Cox CF, Suzuki S. Re-evaluating pulpal protection: calcium hydroxide liners vs cohe-sive hybridization. J Am Dent Assoc 1994;125:823–31.

46. Murray PE, Hafez AA, Smith AJ, Cox CF. Identification of hierarchical factors to guideclinical decision making for successful long-term pulp capping. Quintessence Int2003;34:61–70.

47. Junn DJ, McMillan P, Bakland LK, Torabinejad M. Quantitative assessment of dentinbridge formation following pulp-capping with mineral trioxide aggregate (MTA). JEndod 1998;24:278.

48. Pitt-Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP. Usingmineral trioxide aggregate as a pulp-capping material. J Am Dent Assoc1996;127:1491– 4.

49. Thomson TS, Berry JE, Somerman MJ, Kirkwood KL. Cementoblasts maintain expres-sion of osteocalcin in the presence of mineral trioxide aggregate. J Endod2003;29:407–12.

50. Sarkar NK, Caicedo R, Ritwik R, Moiseyeva R, Kawashima I. Physiochemical basis ofthe biologic properties of mineral trioxide aggregate. J Endod 2005;31:97–100.

51. Schmitt D, Lee J, Bogen G. Multifaceted use of Pro Root MTA root canal repairmaterial. Pediatr Dent 2001;23:326 –30.

52. Mejare I, Cvek M. Partial pulpotomy in young permanent teeth with deep cariouslesions. Endod Dent Traumatol 1993;9:238 – 42.

53. Hernandez R, Bader S, Boston D, Trope M. Resistance to fracture of endodonticallytreated premolars restored with new generation dentin bonding systems. Int EndodJ 1994;27:281– 4.

54. Katebzadeh N, Dalton BC, Trope M. Strengthening immature teeth during and afterapexification. J Endod 1998;24:256 –9.

55. Lawley GR, Schindler WG, Walker WA, Kolodrubetz D. Evaluation of ultrasonicallyplaced MTA and fracture resistance intracanal composite resin in a model of apexi-fication. J Endod 2004;30:167–72.

56. Goldberg F, Kaplan A, Roitman M, Manfre S, Picca M. Reinforcement effect of a resinglass ionomer in the restoration of immature roots in vitro. Dent Traumatol2002;18:70 –2.

57. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth withapical periodontitis and sinus tract. Dent Traumatol 2001;17:185–7.

58. Banchs F, Trope M. Revascularization of immature permanent teeth with apicalperiodontitis: new technique protocol? J Endod 2004;30:196 –200.

Pulp Symposium


Regenerative Potential of Dental PulpMartin Trope, DMD

AbstractThe regenerative potential of dental pulp, particularly inmature teeth, has been considered extremely limited.However, our improved understanding of pulpal inflam-mation and repair and improved dental materials andtechnologies make vital pulp therapy a viable alterna-tive to root canal treatment. This article explores ourknowledge in this regard and the future potential ofsaving or even regenerating the pulp as a routinedental procedure. (J Endod 2008;34:S13-S17)

Key WordsPulp, regeneration, revascularization, vital

The Importance of Vital PulpAlthough it is easy to understand the value of a vital pulp when the tooth is

immature and underdeveloped, it is also important to understand its value in a fullyformed tooth. Endodontic disease is apical periodontitis, and as such, the biologicrationale for endodontics is the prevention or treatment of apical periodontitis. Forapical periodontitis to be present, the root canal must contain a necrotic infected pulp(1). Therefore, the vital (noninfected) pulp ensures no apical periodontitis. Thus,maintaining the vital pulp prevents apical periodontitis, and the potential to regeneratean injured or necrotic pulp would be the best root filling possible.

The Pulp’s Regenerative PotentialThe Unexposed Pulp

The inflamed pulp unexposed by caries or trauma always has the potential to berepaired. Although our diagnostic ability to differentiate a vital from a necrotic pulp isgood, differentiating between reversibly and irreversibly inflamed pulp remains aneducated guess at best (2). We do know, however, that the younger the pulp, the betterits repair potential.

The Exposed PulpTreatment of the exposed pulp remains quite controversial, with different ap-

proaches endorsed by different dental specialties. Vital therapy (ie, pulp capping, par-tial or full pulpotomy) on traumatically exposed pulps is very successful (3), whereasvital pulp therapy on the cariously exposed tooth is not nearly as successful (4). Thedifference in success rates is explained by the status of the pulp at the time of theprocedure (Fig. 1). Capping the healthy pulp gives very high success rates, whereascapping the inflamed pulp results in lower and less predictable success (Fig. 2) (5, 6, 7).On the other hand, with a carious exposure the area and depth of inflammation are veryunpredictable, and pulp capping at the superficial exposure site is popular. Thus, it isvery likely that we would be capping an inflamed pulp, and more failures (necroticpulps) would result.

Another extremely important factor in the success of treating a vital exposure is thecoronal seal after the pulp capping/pulpotomy (8). Cox et al. (8) showed that the pulpcan withstand the toxicity of most dental materials, and that what was previously inter-preted as toxicity was, in fact, due to the material not sealing adequately. Therefore, it isconsidered essential that a well-sealed coronal seal be placed over the vital pulp ther-apy. This is considered much more important than the material used on the vital pulp.

Approaches to Treatment of Carious Exposurein the Immature Tooth

Pediatric DentistryBecause the young vital pulp has such good potential for repair, it is considered

reasonable to perform an indirect or direct pulp cap on a carious exposure as long asa good coronal restoration can be placed (9). The rationale for this approach is thatmost young pulps can heal as long as the coronal restoration does not allow leakage ofadditional inflammatory stimulants or microorganisms.

EndodonticsPulpal inflammation is usually superficial and is unlikely to extend past the canal

orifices, and the healing potential is good if a healthy pulp is treated. Hence, the optimalapproach is to perform a full pulpotomy (thus removing the coronally inflamed pulp)and treating the presumably healthy pulp at the canal orifices. When the root canal has

From private practice, Philadelphia, Pennsylvania.Address requests for reprints to Martin Trope, DMD, 1601

Walnut St, Suite 402, Philadelphia, PA 19102. E-mail address:[email protected].

Conflict of Interest: Martin Trope, DMD, reports no finan-cial interests or potential conflicts of interest.0099-2399/$0 - see front matter



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JOE — Volume 34, Number 7S, July 2008 Regenerative Potential of Dental Pulp S13

developed thick dentinal walls and the apices are closed, a full pulpec-tomy can be performed (Fig. 3).

Revascularization of Infected Pulp SpacePulp Revascularization

Revascularization of an immature necrotic tooth has many poten-tial advantages.

It has been shown that under certain conditions revascularizationcan be achieved in young teeth that have been traumatically avulsed,leaving a necrotic but uninfected pulp. Skoglund et al. (10) demon-strated that in extracted dog teeth, pulpal revascularization started im-mediately after reimplantation and was completed after approximately45 days (Fig. 4). It is important to understand the biologic featurespermitting revascularization in young avulsed teeth, so that we mightattempt to reproduce these unique conditions when the pulp space isinfected. The immature avulsed tooth has an open apex, short root, andintact but necrotic pulp tissue. Therefore, the new tissue has easy accessto the root canal system and a relatively short distance for proliferationto reach the coronal pulp horns. It has been experimentally shown thatthe apical portion of a pulp might remain vital and proliferate coronallyafter reimplantation, replacing the necrotized coronal portion of thepulp (11–13). The speed with which the tissue completely revascular-izes the pulp space is important because bacteria from the outside arecontinually attempting to enter the pulp space, and the presence of vitalpulpal tissue greatly slows or prevents the bacterial penetration into thistissue compartment. The ischemically necrotic pulp that is unique to anavulsion injury acts as a scaffold into which the new tissue grows, and the

fact that the crown is usually intact (rather than carious or with an accesscavity) slows bacterial penetration because their only access to the pulp isthrough cracks (14) or enamel defects. Thus, the race between prolifera-tion of new tissue and infection of the pulp space favors the new tissue.

Revascularization of the pulp space in a necrotic, infected toothwith apical periodontitis was attempted by Nygaard-Ostby and Hjortdal(15) in the 1960s but was mostly unsuccessful. However, the materialsand instruments available 40 –50 years ago were probably not sufficientto create an environment similar to the avulsed tooth, ie, a canal that isfree of bacteria, containing a scaffold for new tissue to grow and to belargely resistant to further bacterial penetration. With currently avail-able technologies it could be possible to effectively disinfect an infectedpulp, artificially place a scaffold, and then effectively seal the accesscavity to resist subsequent infection.

A recent case report by Banchs and Trope (16) has reproducedresults in cases reported by others, indicating that it might be possible toreplicate the unique circumstances of an avulsed tooth to revascularizethe pulp in infected necrotic immature roots (11–13). Our case (Fig. 5)described the treatment of an immature second lower right premolarwith radiographic and clinical signs of apical periodontitis with thepresence of a sinus tract. The canal was disinfected without mechanicalinstrumentation but with copious irrigation with 5.25% sodium hypo-chlorite and the use of a mixture of ciprofloxacin, metronidazole, andminocycline (17), mixed as described in Fig. 6.

A blood clot was produced to the level of the cementoenameljunction to provide a scaffold for the ingrowth of new tissue followed bya double seal of mineral trioxide aggregate in the cervical area and abonded resin coronal restoration above it. Clinical and radiographicevidence of healing was observed as early as 22 days. The large radi-olucency had disappeared within 2 months, and at the 24-month recallit was obvious that the root walls were thick, and the development of the rootbelow the restoration was similar to the adjacent and contralateral teeth.

The antibacterial effectiveness of the triantibiotic paste reported byHoshino et al. (17) was confirmed by our group in a dog model withinfected immature roots (18). In addition, our group demonstrated indogs that the potential for revascularization does exist (Fig. 7), and thatthe blood clot was essential as a scaffold (19). At this point, we areunsure of which factors in the blood clot are important. When thesefactors are isolated, they can be incorporated into a synthetic scaffoldthat will be easier to for clinicians to manipulate compared with a bloodclot.

The procedure described in this section can be attempted in mostcases. If no signs of regeneration are present after 3 months, then moretraditional treatment methods can be initiated.

Figure 1. Histologic section of a pulp after a traumatic exposure 24 hourspreviously. Only about 1 mm of superficial pulp is inflamed.

Figure 2. Carious exposure caused by caries. The underlying inflamed pulp is removed, and a partial pulpotomy is performed on the remaining healthy pulp withcalcium hydroxide (Courtesy Dr. Francisco Banchs).

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S14 Trope JOE — Volume 34, Number 7S, July 2008

Figure 3. In this case a full pulpotomy was performed (thus removing the coronally inflamed pulp) and treating the presumably healthy pulp at the canal orifices. Whenthe root canal has developed thick dentinal walls and the apices are closed, a full pulpectomy can be done (Courtesy Dr. Francisco Banchs).

Figure 4. Revascularization of immature dog teeth during period of 45 days. The teeth were extracted and immediately replanted. During the course of 45 days theblood supply moves into the pulp space.

Pulp Symposium


Figure 5. Immature tooth with a necrotic infected canal with apical periodontitis. The canal is disinfected with copious irrigation with sodium hypochloriteand triantibiotic paste. After 4 weeks the antibiotic is removed, and a blood clot is created in the canal space. The access is filled with a mineral trioxideaggregate base and bonded resin above it. At 7 months the patient is asymptomatic, and the apex shows healing of the apical periodontitis and some closureof the apex. Reproduced with permission from Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatmentprotocol? J Endod 2004;30:196-200.

Figure 6. Composition and mixing instructions for the triantibiotic paste (adapted from Hoshino et al. (17)).

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There has been a great deal of discussion as to the correct termi-nology for what has been called pulp revascularization in this article.Some have used the cases shown as examples of pulp regeneration andthe beginning of stem cell technology in endodontics. It is clearly notapexification because not only the apex is closed, but the canal walls arethicker as well. Apexogenesis accomplishes a closed apex and thickerdentinal walls but by definition uses remaining vital root pulp to attainthis goal, which is not the case here. Guided tissue regeneration hasbeen used in periodontics and has some merit. However, guided tissueregeneration in periodontics assumes regeneration of periodontalstructures, yet this is not the case for pulp. In the present cases, we mustdistinguish between revascularization and pulp regeneration. Presently,we can only say with certainty that the pulp space has returned to a vitalstate. On the basis of research in avulsed teeth and a recent study oninfected teeth, however, it is more likely that the tissue in the pulp spaceis similar to a periodontal ligament than to pulp tissue (19). It appearsthat there is approximately a 30% chance of pulp tissue reentering thepulp space (20). Future research will need to be performed to stimulatepulp regeneration from the pluripotential cells in the periapical region(21).

References1. Bergenholtz G. Micro-organisms from necrotic pulps of traumatized teeth. Odont

Revy 1974;25:347–58.2. Dummer PM, Hicks R, Huws D. Clinical signs and symptoms in pulp disease. Int

Endod J 1980;13:27–35.3. Cvek M. A clinical report on partial pulpotomy and capping with calcium hy-

droxide in permanent incisors with complicated crown fracture, J Endod1978;4:232–7.

4. Barthel CR, Rosenkranz B, Leuenberg A, Roulet JF. Pulp capping of carious expo-sures: treatment outcome after 5 and 10 years: a retrospective study. J Endod2000;26;525– 8.

5. Tronstad L, Mjor IA. Capping of the inflamed pulp. Oral Surg 1972;34:477– 83.6. Mjor IA, Tronstad L. The healing of experimentally induced pulpitis. Oral Surg

1974;38:115–9.

7. Cvek M, Cleaton-Jones PE, Austin JC, Andreasen JO. Pulp reactions to exposureafter experimental crown fractures or grinding in adult monkeys, J Endod1982;8:391–9.

8. Cox CF, Keall HJ, Ostro E, Bergenholtz G. Biocompatibility of surface-sealed dentalmaterials against exposed pulps. Prosthet Dent 1987;57:1–9.

9. Sato T, Hoshino E, Uematsu H, Noda T. In vitro antimicrobial susceptibility to com-binations of drugs on bacteria from carious and endodontic lesions of human de-ciduous teeth. Oral Microbiol Immunol 1993;8:172– 6.

10. Skoglund A, Tronstad L, Wallenius K. A microradiographic study of vascular changesin replanted and autotransplanted teeth in young dogs. Oral Surg Oral Med OralPathol 1978;1:172– 8.

11. Barrett AP, Reade PC. Revascularization of mouse tooth isografts and allo-grafts using autoradiography and carbon-perfusion. Arch Oral Biol 1981;26:541–5.

12. Rule DC, Winter GB. Root growth and apical repair subsequent to pulpal necrosis inchildren. Br Dent J 1966;120:586 –90.

13. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature perma-nent tooth with apical periodontitis and sinus tract. Dent Traumatol 2001;17:185–7.

14. Love RM. Bacterial penetration of the root canal of intact incisor teeth after a simu-lated traumatic injury. Endod Dent Traumatol 1996;12:289 –93.

15. Nygaard-Ostby B, Hjortdal O. Tissue formation in the root canal following pulpremoval. Scand J Dent Res 1971:79:333– 48.

16. Banchs F, Trope M. Revascularization of immature permanent teeth with apicalperiodontitis: new treatment protocol? J Endod 2004;30:196 –200.

17. Hoshino E, Kurihara-Ando N, Sato I, et al. In-vitro antibacterial susceptibility ofbacteria taken from infected root dentine to a mixture of ciprofloxacin, metronida-zole and minocycline. Int Endod J 1996;29:125–30.

18. Windley W III, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immatureteeth with a triple antibiotic paste. J Endod 2005;6:439 – 43.

19. Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization ofimmature dog teeth with apical periodontitis. J Endod 2007;33:680 –9.

20. Ritter AL, Ritter AV, Murrah V, Sigurdsson A, Trope M. Pulp revascularization ofreplanted immature dog teeth after treatment with minocycline and doxycyclineassessed by laser Doppler flowmetry, radiography, and histology. Dent Traumatol2004;20:75– 84.

21. Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and itsresiding stem cells from human immature permanent teeth: a pilot study. J Endod2008;34:166 –71.

Figure 7. Revascularization of an immature dog tooth with apical periodontitis. The root was artificially infected, producing apical periodontitis. After treatmentsimilar to that described in Fig. 5, revascularization has occurred.

Pulp Symposium


Vital Pulp Therapy with New Materials for Primary Teeth:New Directions and Treatment PerspectivesAnna B. Fuks, CD

AbstractVital pulp therapy aims to treat reversible pulpal injuryand includes 2 therapeutic approaches: (1) indirect pulptreatment for deep dentinal cavities and (2) direct pulpcapping or pulpotomy in cases of pulp exposure. Indi-rect pulp treatment is recommended as the most ap-propriate procedure for treating primary teeth withdeep caries and reversible pulp inflammation, providedthat this diagnosis is based on a good history, a properclinical and radiographic examination, and that thetooth has been sealed with a leakage-free restoration.Formocresol has been a popular pulpotomy medica-ment in the primary dentition and is still the mostuniversally taught pulp treatment for primary teeth.Concerns have been raised over the use of formocresolin humans, and several alternatives have been pro-posed. Controlled clinical studies have been criticallyreviewed, and mineral trioxide aggregate and ferricsulfate have been considered appropriate alternativesto formocresol for pulpotomies in primary teeth withexposed pulps. In most of the studies reviewed, thecaries removal method has not been described. The useof a high-speed handpiece or laser might result in anexposure of a “normal” pulp that would otherwise notbe exposed. (J Endod 2008;34:S18-S24)

Key WordsFerric sulfate, formocresol, mineral trioxide aggregate,primary teeth, pulp therapy

The aim of vital pulp therapy is to treat reversible pulpal injuries in both permanentand primary teeth, maintaining pulp vitality and function (1). In addition to these, in

primary teeth it is important to preserve the tooth until its natural exfoliation time, thuspreserving arch integrity (2). Vital pulp therapy includes 2 therapeutic approaches:indirect pulp treatment (IPT) in cases of deep dentinal cavities and direct pulp capping(DPC) or pulpotomy in cases of pulp exposure (1).

Advances in biomedical research open avenues for the design of new methods ofdental treatment, aiming at regeneration of the dentin-pulp complex. New approacheshave been based on the understanding of the molecular and cellular mechanismsregulating dentinogenesis during dental tissue repair and their potential for clinicalexploitation (1).

The dental pulp possesses the ability to form a dentin-like matrix (tertiary dentin)as part of the repair in the dentin-pulp organ (3). Vital pulp therapy aims to treatreversible pulpal injury in cases in which dentin and pulp are affected by caries, restor-ative procedures, or trauma. Whenever the dentin-pulp complex is affected by injury, 3different physiopathologic conditions might be observed at the dentin-pulp border:

1. In the case of mild injuries as in noncavitated enamel caries or slowly progressingdentinal caries, the odontoblasts might survive, and the odontoblastic layer isstimulated to form a tertiary dentin matrix beneath the injury (reactionary den-tin). Reactionary dentin shows many similarities to the primary and secondarydentin and can effectively oppose exogenous destructive stimuli to protect thepulp (4).

2. With severe dentinal injuries without pulp exposure as in rapidly progressingcarious lesions or in severe tissue damage caused by cavity preparation, odon-toblasts are destroyed subjacent to the affected dentin (5, 6). In an appropriatemetabolic state of the dentin-pulp complex, a new generation of odontoblast-likecells might differentiate and form tubular tertiary dentin (reparative dentinogen-esis) (3, 7). It must be emphasized that under clinical conditions, the matrixformed at the pulp-dentin interface often comprises reactionary dentin, repara-tive dentin, or fibrodentin formation. It is impossible to distinguish these pro-cesses at the in vivo level, and the process might also be indistinguishable from abiochemical and molecular point of view.

3. In the case of pulp exposure, the amputated pulp can be repaired by itself or afterapplication of capping materials (8 –10). Pulp exposure caused by caries showsvery limited potential for pulp recovery as a result of bacterial infection of the pulpfor a substantial period of time, which compromises the defense reaction (11).As part of the wound healing process in the repairing pulp, the dentinogenicpotential of pulp cells can be expressed. Proliferation, migration, and differen-tiation of progenitor cells can give rise to a new generation of reparative dentin-forming cells (odontoblast-like cells), reconstituting the lost continuum at thepulp-dentin border (12, 13).

Indirect Pulp TreatmentAfter this brief review of the cellular changes during tooth development and how

they are mimicked during tissue repair, we are able to assess the biologic validity of thevarious vital pulp treatments. In this light, IPT, contrary to what was believed in the past,can also be an acceptable procedure for primary teeth with reversible pulp inflamma-tion, provided that the diagnosis is based on a good history and proper clinical and

Professor Emeritus, Department of Pediatric Dentistry, Ha-dassah School of Dental Medicine, Hebrew University, Jerusa-lem, Israel.

Address requests for reprints to Dr Fuks at [email protected].

Conflict of Interest: Anna B. Fuks, CD, reports no financialinterests or potential conflicts of interest.0099-2399/$0 - see front matter



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S18 Fuks JOE — Volume 34, Number 7S, July 2008

radiographic examination, and the tooth has been sealed with a leak-age-free restoration (2).

In a recent systematic review on complete or ultraconservativeremoval of decayed tissue, Ricketts et al. (14) concluded that “in deeplesions, partial caries removal is preferable to complete caries removalto reduce the risk of carious exposure.”

Several articles reported the success of this technique in primaryteeth (15–19). On the basis of the biologic changes previously de-scribed and the growing evidence of the success of IPT in primary teeth,we can recommend IPT as the most appropriate treatment for symptom-free primary teeth with deep caries, provided that a proper, leakage-freerestoration can be placed. This issue will be discussed in greater detailfurther in this symposium.

Direct Pulp CappingDPC is carried out when a healthy pulp has been inadvertently

exposed during an operative procedure. The tooth must be asymptom-atic, and the exposure site must be pinpoint in diameter and free of oralcontaminants. A calcium hydroxide medicament is placed over the ex-posure site to stimulate dentin formation and thus “heal” the wound andmaintain the pulp’s vitality (20).

DPC of a carious pulp exposure in a primary tooth is not recom-mended but can be used with success on immature permanent teeth.DPC is indicated for small mechanical or traumatic exposures whenconditions for a favorable response are optimal. Even in these cases, thesuccess rate is not particularly high in primary teeth. Treatment failuremight result in internal resorption or acute dentoalveolar abscess (20).

Presently, DPC should still be looked on with some reservations inprimary teeth. This treatment, however, could be recommended forexposed pulps in older children 1 or 2 years before normal exfoliation.In these children, a failure of treatment would not imply the need for aspace maintainer after extraction, as it would in younger children.

In a recent article, Caicedo et al. (21) demonstrated good pulpresponse in primary teeth after DPC or pulpotomy with MTA and con-cluded that MTA might be a favorable material for pulp capping andpulpotomy in primary teeth.

PulpotomyPulpotomy is still the most common treatment for cariously ex-

posed pulps in symptom-free primary molars. The aim of this treatmentis to preserve the radicular pulp, avoiding pain and swelling, and ulti-mately to retain the tooth, preserving arch integrity (2). Formocresol(FC) has been a popular pulpotomy medicament in the primary denti-tion for the past 70 years since its introduction by Sweet in 1932, and itis still considered the most universally taught and preferred pulp treat-ment for primary teeth (22–24). Concerns have been raised over theuse of FC in humans, mainly as a result of its toxicity and potentialcarcinogenicity (25–32).

The International Agency for Research on Cancer classified form-aldehyde as carcinogenic for humans in June 2004, leaving the profes-sion to look for other alternatives to FC (31). On the basis of the infor-mation available, an expert working group has determined that there isnow sufficient evidence that formaldehyde causes nasopharyngeal can-cer in humans, a rare cancer in developed countries, limited evidencefor cancer of the nasal cavity and paranasal sinuses, and “strong but notsufficient evidence” for leukemia.

There has been a significant amount of discussion in the dentalliterature about the appropriateness and safety of using aldehyde-basedproducts in pediatric dentistry (29). FC is no longer used in somecountries, mainly as a result of safety concerns.

Milnes (33) published an extensive and detailed review of themore recent research on the metabolism, pharmacokinetics, and car-cinogenicity of formaldehyde and concluded that formaldehyde is not apotent human carcinogen under conditions of low exposure. He con-cluded that extrapolation of these research results to pediatric dentistrysuggests an inconsequential risk of carcinogenesis associated withformaldehyde use in pediatric pulp therapy.

In a case-control study in which FC pulpotomies were performedin 5- to 10-year-old children, blood samples were taken before (con-trol) and after treatment to observe the mutagenic potential of FC onlymphocytes cultures. No statistically significant differences could beobserved in the cultured lymphocytes. FC was mutagenic for one patient,however, leading the authors to raise doubts about the desirability ofusing this technique in children (34).

No correlation between FC pulpotomies and cancer has ever beendemonstrated. Nevertheless, several studies have reported that the clin-ical success of FC pulpotomies decreases with time, and the histologicresponse of the primary pulp is “capricious,” ranging from chronicinflammation to necrosis (35).

Presently, there are several pulp dressing medicaments that havebeen proposed to maintain radicular pulp vitality that are equal to, if notbetter than, FC and can be used as alternatives to pulpotomies in pri-mary teeth. The pulp dressing materials and techniques proposed in-clude: electrosurgery (36, 37), laser (38, 39), glutaraldehyde (GT)(40 – 44), calcium hydroxide (CH) (45– 47), freeze-dried bone (48),bone morphogenetic protein (49), osteogenic protein (50), ferric sul-fate (FS) (51–56), mineral trioxide aggregate (MTA) (24, 57–59), andsodium hypochlorite (60).

Although a considerable number of clinical trials and laboratoryanimal studies have been published on this subject, the Cochrane reviewfound that evidence is lacking to conclude which is the most appropriatetechnique for pulpotomies in primary teeth (61). The Cochrane reviewassessment is extremely rigorous, and with the exception of 3 articles,none of the articles evaluated could meet the criteria and were ex-cluded.

Evidence-Based Analysis of Pulpotomy LiteratureLoh et al. (62) published an evidence-based assessment of FC

versus FS by using a different sieving system including all suitable clin-ical trials, not only randomized ones. They concluded that both mate-rials were likely to produce similar clinical/radiographic success.

Following Cochrane’s criticism regarding the paucity of appropri-ately designed, statistically assessed investigations and the lack of long-term outcomes, many studies have been reported, and several othershave begun to contribute to the literature (32).

Fuks and Papagiannoulis (63) assessed the relevant articles thathave appeared after the aforementioned reviews by using the clinicallybased criteria listed by Curzon and Toumba (64). In this review, theMEDLINE search used generated a total of 358 citations, and the sievingof these articles was conducted by examining the article title and assess-ing its relevance (62).

All articles were graded according to the aforementioned criteriaand classified as A if the article met 90% or more of the criteria; B1 if anarticle scored from 75%– 89%; B2 if it scored between 60%–74%; andC if it scored 59% or less, which meant that it had to be excluded. Evenwith different weights attributed to the evaluated articles, no conclusioncould be reached as to the optimum treatment or technique for pulpallyinvolved primary teeth. In a meta-analysis to compare the clinical andradiographic effects of MTA with FC, Peng et al. (65) reported that MTAwas superior to FC. These authors claimed that MTA induces less unde-sirable responses and might be a suitable replacement for FC.

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In another meta-analysis that included clinical trials and random-ized, clinical trials, Deery (66) concluded that pulpotomies performedwith either FS or FC were likely to produce similar results.

Although meta-analysis generally pools data from randomized,clinical trials, they are regarded as observational studies of evidence(67– 69). Usually the reviewer identifies the relevant studies from theliterature and decides whether to include or exclude them. Therefore,the strength of conclusions drawn from a meta-analysis might only becomparable to that drawn from observational studies, which are open tovarious forms of bias. Problems, including publication bias and thevariable quality of the primary studies, can threaten the validity of meta-analysis (70). Another limitation of meta-analyses is that they all searchfor relevant articles in electronic databases and are limited to the En-glish language. Most databases date only from 1965. For this reasonarticles that could have been relevant, particularly on CH or FC pulpo-tomies, were not included. Language bias can also occur because re-searchers whose native language is not English are more likely to pub-lish nonsignificant results in non-English journals and significant resultsin English journals (70).

One of the aims of evidence-based dentistry is to reach an evi-dence-based conclusion and then translate it into a clinical decision thatwould result in a better treatment outcome. With these points in mind,this article will consist of critically assessing the randomized and non-randomized human clinical trials that resulted from a MEDLINE search.This search generated a total of 358 citations, as described by Fuks andPapagiannoulis (63), with the addition of the relevant studies publishedafter that date. Duplicate publications of the same study were excluded.The articles assessed will be limited to the comparisons of FS, MTA, andCH with FC and are presented in Tables 1–3.

Studies Comparing MTA With FCCuisia et al. (2001)71

This randomized, clinical trial compared MTA with FC, but therandomization method was not reported. Only asymptomatic molarswithout clinical and/or radiographic evidence of pulp degenerationwere included. Pulpotomies were performed in 60 molars by 1 pediat-ric dentist using a local anesthetic and restored with a stainless steel

crown, but there was no mention of the use of a rubber dam. The resultswere assessed by 2 pediatric uncalibrated dental residents at 6-monthfollow-up; the clinical success rate was 93% for FC and 97% for MTA,whereas the radiographic success was 77% for FC and 93% for MTA.

Agamy et al. (2004)57

This randomized, clinical trial compared gray MTA, white MTA,and FC in 72 molars of 24 children. Only restorable molars withoutclinical and/or radiographic evidence of pulp degeneration were in-cluded. Each child had at least 3 molars with severe carious involvementand received pulpotomies with all 3 medicaments. An additional 15carious teeth planned for serial extractions after 6 months were selectedfor the histologic part of the study. All pulpotomies were performed bythe same pediatric dentist, and outcome assessment after 12 monthswas done by 2 “blinded” pediatric dentists. Four children (12 molars)dropped out, and of the remaining 60 teeth in 20 patients, 1 (gray MTA)exfoliated normally, and another 6 teeth (4 white MTA and 2 FC) failedas a result of abscesses. The remaining 53 teeth appeared to be clinicallyand radiographically successful. In the histologic study, both types ofMTA formed thick dentin bridges, but the gray MTA appeared to bebetter than white MTA and FC as a pulp dressing, because it presentedthe closest to normal pulp architecture.

Jabbarifar et al. (2004)72

This randomized, clinical trial compared MTA with FC in 64 mo-lars assigned to 2 groups by the toss of a coin. The number of pediatricdentists who performed the treatments was not specified, rubber damisolation was not reported, and all the teeth were restored with SSCs. Out-come assessment of 64 molars remaining at 12 months was done by 2“blinded” pediatric dentists. The number of molars treated at the baselineand the number of dropouts were not reported. Clinical and radiographicsuccess for MTA was 94% and for FC was 91%.

Farsi et al. (2005)59

This randomized, clinical trial compared MTA with FC in 120 mo-lars of 100 children assigned to 2 groups by the toss of a coin. Onlyrestorable molars without clinical and/or radiographic evidence of pulp

TABLE 2. Articles Comparing Directly FS and FC

Direct comparisonarticles: FC � FS

Molars,FC (N)

Molars, FS(N)

Success(clinical), FC

Success(clinical), FS

Success(x-ray), FC

Success(x-ray), FS Follow-up

(mo)N (%) N (%) N (%) N (%)

Fei et al. (1991) 27 29 26 (96) 29 (100) 22 (81) 28 (97) 12Fuks et al. (1997) 37 55 31 (84) 51 (93) 27 (73) 41 (93) 35Aktoren and Gencay (2000) 24 24 21 (88) 21 (88) 19 (80) 20 (84) 24Papagiannoulis (2002) 60 73 58 (97) 66 (90) 47 (78) 54 (74) 36Ibrevic and Al-Jame (2003) 80 84 78 (97) 81 (96) 75 (94) 77 (92) 42–48Huth et al. (2005) 48 49 46 (96) 49 (100) 43 (90) 42 (86) 24Markovic et al. (2005) 33 37 30 (91) 33 (89) 28 (85) 30 (81) 18

FC, formocresol; FS, ferric sulfate.

TABLE 1. Articles Directly Comparing MTA and FC

Direct comparisonarticles: MTA � FC

Molars,FC (N)

Molars,MTA (N)


Success(clinical), MTA

Success(x-ray), FC

Success(x-ray), MTA Follow-up

(mo)N (%) N (%) N (%) N (%)

Cuisia et al. (2001) 30 30 28 (93) 29 (97) 23 (77) 28 (93) 6Agamy et al. (2004) 20 19 18 (90) 19 (100) 18 (90) 19 (100) 12Jabbarifar et al. (2004) 32 32 29 (91) 30 (94) 29 (91) 30 (94) 12Farsi et al. (2005) 36 38 35 (97) 38 (100) 31 (86) 38 (100) 24Holan et al. (2005) 29 33 24 (83) 32 (97) 24 (83) 32 (97) �74Naik and Hegde (2005) 23 24 23 (100) 24 (100) 23 (100) 24 (100) 6

FC, formocresol.

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degeneration were included. The number of pediatric dentists who per-formed the treatments was not specified, rubber dam isolation was notreported, and all the teeth were restored with SSCs. At 24 months, 46molars (38%) were lost, leaving 74 molars for evaluation. All the MTA-treated molars were successful clinically and radiographically (100%). Forthe FC, clinical and radiographic success was 97% and 86%, respectively.

Holan et al. (2005)24

This randomized, clinical trial compared MTA with FC in 64 mo-lars of 35 children assigned to 2 groups by the toss of a coin. Thenumber of operators was not specified, and in 56 molars SSCs wereplaced, 1 molar received a composite restoration, and the other 7 teethwere restored with amalgam. Clinical outcomes were assessed by 1pediatric dentist without “blinding.” Radiographs were assessed by 3“blinded” pediatric dentists using a standardized evaluation form forcalibration (complete agreement for all cases). Internal resorption wasconsidered a failure only when it reached the bone. Arrested internalresorption, calcific metamorphosis, and pulp canal obliteration werenot considered failures.

At 74 months, 2 molars (3%) were lost, leaving 62 molars forevaluation. Clinical and radiographic success was 97% for MTA and83% for FC, respectively.

Naik and Hegde (2005)58

This randomized, clinical trial compared MTA with FC in 50 mo-lars assigned randomly (method not specified) to 2 groups. The inclu-sion criterion was “asymptomatic deep carious lesion with no frankexposure.” Pulpotomies were performed by a postgraduate dentist un-der local anesthesia and rubber dam. It was not clear whether preop-erative radiographs were taken and SSCs were placed 24 hours later.Three teeth were lost to follow-up (2 FC and 1 MTA), and all the re-maining teeth were clinically and radiographically successful at the6-month follow-up.

Studies Comparing FS With FCFei et al. (1991)51

This randomized, clinical trial compared FS wth FC in 83 molars in62 children assigned by a table of random numbers to 2 groups. Onlyrestorable molars without clinical or radiographic signs of pulpal de-generation were included. Teeth with pulpal hemorrhage persistingafter 2 applications of FS or FC were eliminated. A pediatric dentistrypostgraduate student performed all pulpotomies, and 2 pediatric den-tists were “blinded” and calibrated before radiographic assessment. At12 months, 27 molars were lost, leaving 56 molars for assessment.Clinical success for FC was 96% and for FS was 100%; radiographicsuccess was 81% for FC and 97% for FS.

Fuks et al. (1997)52

This randomized, clinical trial compared FS with FC in 96 molarsin 72 children assigned to 2 groups by a toss of a coin. Only asymptom-atic and restorable molars without clinical and radiographic signs ofpulp degeneration were included. Three pediatric dentists performed

the pulpotomies under a local anesthetic and with a rubber dam, butoutcome assessors were not reported. Molars with pulp canal obliter-ation (PCO) were not considered failures. The dropout rate was 4%(4/96 molars) after 6 –34 months. Clinical success for FC was 84% andfor FS was 93%; radiographic success was 80% for FC and 93% for FS.No statistical difference was observed between the 2 groups.

Aktoren and Gencay (2000)73

This randomized, clinical trial compared FS, FC, and GT. Onlyasymptomatic and restorable molars without clinical and radiographicsigns of pulp degeneration were included. Clinicians performing thepulpotomies and outcome assessors were not described. At 24 months,clinical success rates for 72 molars were reported to be 88% for both FCand FS, and radiographic success was 80% for FC and 84% for FS.

Papagiannoulis (2002)74

This randomized, clinical trial compared FS with FC in 133 molarsin 90 children assigned to 2 groups by a toss of a coin. Only asymptom-atic and restorable molars without clinical and radiographic signs ofpulp degeneration were included. Pulpotomies were performed by 3pediatric dentists; most molars were restored with SSCs, and a fewreceived composite resin restorations. Outcomes were assessed by aseparate “blinded” pediatric dentist. Molars with PCO or nonprogres-sive internal resorption were not considered failures. Clinical successwas 97% for FC and 90% for FS, and radiographic success was 78% forFC and 74% for FS.

Ibrevic and Al-Jame (2003)54

This randomized, clinical trial compared FS with full-strength FC in194 molars in 70 patients allocated alternately to 2 groups. Only restor-able molars without clinical and radiographic signs of pulp degenera-tion were included. Pulpotomies were performed by 1 pediatric dentist,and most molars received SSCs; a few molars were restored with amal-gam. Clinical outcomes were assessed by the operator, but radiographicoutcomes were assessed by both the operator and another “blinded”evaluator. Calibration was not reported, but both assessors reachedconsensus on radiographic outcomes. Ten patients (30 molars)dropped out after 42 months. Clinical success rates were 97% in the FCgroup and 96% in the FS group. The radiographic success rate was 94%in the FC group and 92% in the FS group. No statistical differences werefound between the radiographic assessments of both pulpotomy agents.

Huth et al. (2005)47

This randomized, clinical trial compared FS, FC, CH, and laser in107 children. A power calculation estimated the numbers of molarsrequired to achieve statistical significance. Randomization was done bycasting a concealed lot from a box of 4 � 50 lots, such that 200 molarswere allocated to 4 groups. Only asymptomatic restorable molars with-out clinical and radiographic signs of pulp degeneration were included.The molars received SSCs or composite resin restorations. Two pediat-ric dentists performed the pulpotomies under local or general anesthe-sia and rubber dam, and 2 other “blinded” experienced dentists per-

TABLE 3. Articles Directly Comparing CH and FC

Direct comparisonarticles: FC � CH

Molars,FC (N)

Molars,CH (N)


Success(clinical), CH

Success(x-ray), FC

Success(x-ray), CH Follow-up (mo)

N (%) N (%) N (%) N (%)

Waterhouse et al. (2000) 44 35 37 (84) 27 (77) 37 (84) 27 (77) To exfoliationHuth et al. (2005) 48 38 46 (96) 33 (87) 43 (90) 25 (66) 24Markovic et al. (2005) 33 34 30 (91) 28 (82) 28 (85) 26 (76) 18

FC, formocresol; CH, calcium hydroxide.

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formed outcome assessments. Intraexaminer and interexaminerreproducibility was optimal (K � 1.0). The dropout rate was 8% (16/191 molars), and the remaining participants were examined after 24months. Clinical success rate was 96% for FC and 100% for FS, andradiographic success was 90% for FC and 86% for FS.

Markovic et al. (2005)56

This randomized, clinical trial compared FS, FC, and CH in 104molars in 104 children assigned randomly to 3 groups. Vital carious-exposed molars with no radiographic signs of pulpal degeneration wereincluded. Pulpotomies were performed by 3 pediatric dentists, andoutcomes were assessed by a separate evaluator. The intraexamineragreement was moderate (K � 0.70). The number of molars at baselineand the number of dropouts were not reported. The clinical success rateat 18 months for FC was 91%, for FS was 89%, and for CH was 82%. Theradiographic success was 85% for FC, 82% for FS, and 76% for the CHgroup. These differences, however, were not statistically significant.

Studies Comparing CH With FCThree articles compared directly CH with FC. Two of them have

been summarized previously (47, 56).

Waterhouse et al. (2000)75

This randomized, clinical trial compared FC and CH in 84 molarsin 52 children assigned to 2 groups by the toss of a coin. Only healthychildren with restorable molars without clinical and radiographic signsof pulp degeneration were included. Pulpotomies were performed byclinicians under rubber dam or cotton roll isolation; SSCs were placed“where indicated” (indications not described), and other molars wererestored with amalgam, glass ionomer, or compomer. Outcomes wereassessed by a separate pediatric dentist, “blinded” and calibrated in aparallel study (77% interexaminer agreement). At 22 months, 5 molarsin 3 patients dropped out, leaving 79 molars in 49 children. Clinical andradiographic success was 84% for FC and 77% for CH.

Studies Comparing Laser With FCSaltzman et al. (2005)39

This randomized single-blind, split-mouth clinical trial compareda diode laser pulpotomy with MTA with a conventional FC/zinc oxide–eugenol (ZOE) pulpotomy. A total of 26 pairs of teeth from 16 patientsbetween 3– 8 years old were selected on the basis of clinical and radio-graphic criteria. All teeth were followed up clinically and radiographi-cally for 15 months. A total of 7 laser-MTA–treated teeth were radio-graphic failures, as opposed to 3 FC/ZOE-treated teeth at 15.7 months;however, these results were not statistically significant. The authors sug-gested that an improved success rate among a larger patient sample and alonger follow-up period would be required for the laser-MTA pulpotomy tobe considered a suitable alternative to conventional FC pulpotomy.

Liu JF (2006)76

This clinical study compared the effects of Nd:YAG laser pulpotomywith FC on human primary teeth. Patients without any medically com-promised disease were selected from the patient population at a hospi-tal-based dental clinic in Taiwan. Primary teeth that required pulpotomy“because of carious pulp exposure” were selected for this study. Fiftychildren with an average age of 5 years, 3 months (range, 4 –7 years)participated in the study group, and a total of 68 primary molars weretreated with the Nd:YAG laser. Forty-four children participated in thecontrol group, and 69 primary molars were treated with diluted FC.Follow-up time was between 6 – 64 months. In the Nd:YAG laser group,clinical success was achieved in 66 of 68 teeth (97%), and 94% were

radiographically successful. In the control group, 85% and 78%achieved clinical and radiographic success, respectively. The successrate of the Nd:YAG laser was significantly higher than that of the FCpulpotomy. The permanent successors of the laser-treated teeth eruptedwithout any complications.

Study Comparing Sodium Hypochlorite With FSVargas et al. (2006)60

This prospective randomized, clinical study compared the effec-tiveness of 5% sodium hypochlorite (NaOC1) with that of FS as a pul-potomy medicament in decayed primary molars. Twenty-three healthypatients between 4 and 9 years old with at least 2 primary molarsneeding a pulpotomy were included in the study. The teeth were clini-cally and radiographically examined, and the signs/symptoms were re-corded at 0, 6, and 12 months. Six-month results were based on the first32 teeth in the NaOC1 group and 28 teeth in the FS group. Twelve-monthresults were based on 13 teeth in the FS group and 14 in the NaOC1group. At 6 months, 100% clinical success was found in both the FS andNaOC1 groups. Radiographic success for FS was 68%, with internalresorption being the most common finding. The NaOC1 showed 91%radiographic success. At 12 months, FS had 85% clinical success and62% radiographic success. NaOC1 had 100% clinical success and 79%radiographic success. The authors concluded that preliminary evidenceshowed that NaOC1 can be used successfully as a pulpotomy medicament.

SummaryFrom this review of the randomized, clinical trials, one can ob-

serve that all the studies comparing MTA with FC showed that MTApresented better results, even though in some of them there was nostatistical difference as a result of the small number of teeth tested. FSwas also better than FC in some studies and similar to FC in others, whereasthe 3 studies with CH showed inferior outcomes. It should be emphasized,however, that in most of the studies the method of caries removal has notbeen described. The use of a high-speed handpiece or laser might result inan exposure of a “normal” pulp that would otherwise not be exposed andnot need a pulpotomy or that could be alternatively treated by IPT.

As previously mentioned, one of the aims of evidence-based den-tistry is to reach an evidence-based conclusion and then translate it intoa clinical decision that would result in a better treatment outcome. Itshould be kept in mind, however, that improving patient care requiresthe consideration of other factors including the cost and techniquesensitivity of the new medicament.

From the studies previously presented, MTA showed better resultsin all cases and should be recommended as an alternative to FC. One ofthe drawbacks of this material, however, is its high cost, and its use inpediatric dentistry practice can become almost prohibitive in somecircumstances. Hence, FS can still be considered a valid and inexpen-sive solution for pulpotomies in primary teeth (2).

A recent preliminary evaluation of sodium hypochlorite showedpromising results when compared with FS. The follow-up time, how-ever, is only 1 year. Longer follow-up and more clinical studies areneeded to confirm these results.

References1. Tziafas D. The future role of a molecular approach to pulp-dentinal regeneration.

Caries Res 2004;38:314 –20.2. Fuks AB. Current concepts in vital primary pulp therapy. Eur J Paediatr Dent

2002;3:115–20.3. Baume LJ. The biology of pulp and dentine. In: Myers HM, ed. Monographs in oral

science. Basel, Switzerland: Karger, 1980:67–182.4. Smith AJ, Sloan AJ, Matthews JB, Murray PE, Lumley P. Reparative process in dentine

and pulp. In: Addy M, Embery G, Edgar WM, Orchardson R, eds. Tooth wear andsensitivity. London, UK: Dunitz, 2002:53– 66.

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5. Bjorndal L, Mjor IA. Pulp-dentin biology in restorative dentistry: 4 — dental caries:characteristics of lesions and pulpal reactions. Quintessence Int 2001;32:717–36.

6. Kitamura C, Kimura K, Nakayama T, Toyoshima K, Terashita M. Primary and second-ary induction of apoptosis in odontoblasts after cavity preparation of rat molars. JDent Res 2001;80:1530 – 4.

7. Bjorndal L, Darnnavan T. A light microscopic study of odontoblastic and nonodon-toblastic cells involved in tertiary dentinogenesis in well-defined cavitated cariouslesions. Caries Res 1999;33:50 – 60.

8. Nyborg H. Healing process in the dental pulp on capping: a morphologicstudy— experiments on surgical lesions of the pulp in dog and man. Acta OdontolScand 1955;13(Suppl 16):1–130.

9. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposure on dentalpulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol1965;20:340 –9.

10. Yamamura T. Differentiation of pulpal cells and inductive influences of various ma-trices with reference to pulpal wound healing. J Dent Res 1985;64:530 – 40.

11. Bergenholz G. Factors in pulpal repair after oral exposure. Adv Dent Res 2001;15:84.12. Fitzegerald M, Ghiego JD Jr, Heis R. Autoradiographic analysis of odontoblasts re-

placement following pulp exposures in primate teeth. Arch Oral Biol 1990;35:707–15.

13. Mjor IA, Dahl E, Cox CF. Healing of pulp exposure: an ultrastructural study. J OralPathol Med 1991;20:496 –501.

14. Ricketts DNJ, Kidd EAM, Innes N, Clarkson J. Complete or ultraconservative removalof decayed tissue in unfilled teeth. Cochrane Database Syst Rev 2006;CD003808.

15. Farooq NS, Coll JA, Kuwabara A, Shelton P. Success rates of formocresol pulpotomyand indirect pulp treatment of deep dentinal caries in primary teeth. Pediatr Dent2000;22:278 – 86.

16. Straffon LH, Loos P. The indirect pulp cap: a review and commentary. Isr J Dent Sci2000;17:7–14.

17. Falster CA, Araujo FB, Straffon LH, Nor JE. Indirect pulp treatment: In vivo outcomesof am adhesive resin system vs calcium hydroxide for protection of the dentin-pulpcomplex. Pediatr Dent 2002;24:241– 8.

18. Al-Zayer MA, Straffon LH, Feigal RJ, Welch KB. Indirect pulp treatment of primaryposterior teeth: a retrospective study. Pediatr Dent 2003;25:29 –36.

19. Marchi JJ, de Araujo FB, Froner AM, Straffon LH, Nor JE. Indirect pulp capping in theprimary dentition: a 4-year follow-up study. J Clin Pediatr Dent 2006;31:68 –71.

20. Fuks AB. Pulp therapy for the primary dentition. In: Pediatric dentistry: infancythrough adolescence. St Louis, MO: Elsevier, 2005:11830.

21. Caicedo R, Abbott PV, Alongi DJ, Alarcon MY. Clinical, radiographic and histologicalanalysis of the effects of mineral trioxide aggregate used in direct pulp capping andpulpotomies of primary teeth. Aust Dent J 2006;51:297–305.

22. Primosch RE, Glom TA, Jerrell RG. Primary tooth pulp therapy as taught in predoc-toral pediatric dental programs in the United States. Pediatr Dent 1997;19:118 –22.

23. Vij R, Coll JA, Shelton P, Farooq NS. Caries control and other variables associated withsuccess of primary molar vital pulp therapy. Pediatr Dent 2004;26:214 –20.

24. Holan G, Eidelman E, Fuks AB. Long-term evaluation of pulpotomy in primary molarsusing mineral trioxide aggregate and formocresol. Pediatr Dent 2005;27:129 –36.

25. Auerbach C, Moutschen-Damen M, Moutschen M. Genetic and cytogenetical effects offormaldehyde and related compounds. Mutat Res 1977;39:317– 61.

26. Pruhs RJ, Olen GA, Sharma PS. Relationship between formocresol pulpotomies onprimary teeth and enamel defects on their permanent successors. J Am Dent Assoc1977;94:698 –700.

27. Block RM, Lewis RD, Sheats JB, Burke SG. Antibody formation to dog pulp tissuealtered by formocresol within the root canal. Oral Surg 1978;45:282–92.

28. Myers DR, Shoaf HK, Dirksen TR, Pashley DH, Whitford GM, Reynolds KE. Distribu-tion of 14c formaldehyde after pulpotomy with formocresol. J Am Dent Assoc1978;96:805–13.

29. Judd PL, Kenny DJ. Formocresol concerns: a review. J Can Dent Assoc 1987;53:401– 4.

30. Sun HW, Feigal RJ, Messer HH. Cytotoxicity of glutaraldehyde and formaldehyde inrelation to time of exposure and concentration. Pediatr Dent 1990;12:303–7.

31. International Agency for Research on Cancer. Press release no. 153. Available at:http://www.iarc.fr/ENG/Press_Releases/archives/pr153a.html. Accessed June 15,2004.

32. Srinivasan V, Patchett CL, Waterhouse JP. Is there life after Buckley’s formocresol?part I: a narrative review of alternative interventions and materials. Int J Paediatr Dent2006;16:117–35.

33. Milnes AR. Persuasive evidence that formocresol use in pediatric dentistry is safe.J Can Den Assoc 2006;72:247– 8.

34. Zarzar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Junior LA. Formocresolmutagenicity following primary tooth pulp therapy: an in-vivo study. J Dent2003;31:479 – 85.

35. Rolling I, Thylstrup A. A 3-year follow-up study of pulpotomized primary molarstreated with the formocresol technique. Scand J Dent Res 1975;83:47–53.

36. Fishman SA, Udin RD, Good DL, Rodef F. Success of electrofulguration pulpotomiescovered by zinc oxide and eugenol or calcium hydroxide: a clinical study. PediatrDent 1996;18:385–90.

37. Sasaki H, Ogawa T, Koreeda M, Ozaki T, et al. Electrocoagulation extends the indi-cation of calcium hydroxide pulpotomy in the primary dentition. J Clin Pediatr Dent2002;26:275–7.

38. Elliot RD, Roberts MW, Burkes J, Phillips C. Evaluation of carbon dioxide laser onvital human primary pulp tissue. Pediatr Dent 1999;21:327–31.

39. Saltzman B, Sigal M, Clokie C, et al. Assessment of a novel alternative to conventionalformocresol-zinc oxide eugenol pulpotomy for the treatment of pulpally involvedhuman primary teeth: diode laser-mineral trioxide aggregate pulpotomy. Int J Pae-diatr Dent 2005;15:437– 47.

40. Alacam A. Long-term effects of primary teeth pulpotomies with formocresol, glutar-aldehyde-calcium hydroxide, and glutaraldehyde-zinc oxide eugenol on succedane-ous teeth. J Pedod 1989;18:123–32.

41. Prakash C, Chandra S, Jaiswal JN. Formocresol and pulpotomies in primary teeth.J Pedod 1989;13:314 –22.

42. Fuks AB, Bimstein E, Klein H, Guelmann M. Assessment of a 2% buffered glutaraldehydesolution in pulpotomized primary teeth of schoolchildren. J Dent Child 1990;57:371–5.

43. Shumayrikh NM, Adenubi JO. Clinical evaluation of glutaraldehyde with calciumhydroxide and glutaraldehyde with zinc oxide eugenol in pulpotomy of primarymolars. Endod Dent Traumatol 1999;15:259 – 64.

44. Araujo FB, Ely LB, Pergo AM, Pesce HF. A clinical evaluation of 2% buffered glutar-aldehyde in pulpotomies of human deciduous teeth: a 24-month study. Braz Dent J1995;6:41– 4.

45. Schroder U. A 2-year follow-up of primary molars, pulpotomized with a gentle tech-nique and capped with calcium hydroxide. Scand J Dent Res 1978;86:273– 8.

46. Gruythuysen RJ, Weerheijm KL. Calcium hydroxide pulpotomy with a light-cured,cavity-sealing material after two years. J Dent Child 1997;64:251–3.

47. Huth KC, Paschos E, Hajek-Al-Khatar N, et al. Effectiveness of 4 pulpotomy tech-niques: Randomized controlled trial. J Dent Res 2005;84:1144 – 8.

48. Fadavi S, Anderson AW. A comparison of the pulpal response to freeze-dried bone,calcium hydroxide, and zinc oxide-eugenol in primary teeth in two cynomolgusmonkeys. Pediatr Dent 1996;18:52– 6.

49. Nakashima M. Induction of dentine formation on canine amputated pulp by recom-binant human bone morphogenetic proteins (BMP)-2 and 4. J Dent Res 1994;73:1515–22.

50. Rutherford RB, Wahle J, Tucker M, Roger D, Charette M. Induction of reparativedentine formation in monkeys by recombinant human osteogenicprotein-1. ArchOral Biol 1993;38:571– 6.

51. Fei AL, Udin RD, Johnson R. A clinical study of ferric sulfate as a pulpotomy agent inprimary teeth. Pediatr Dent 1991;13:327–32.

52. Fuks AB, Holan G, Davis JM, Eidelman E. Ferric sulfate vs dilute formocresol inpulpotomized primary molars: long-term follow-up. Pediatr Dent 1997;19:327–30.

53. Smith NL, Seale NS, Nunn ME. Ferric sulfate pulpotomy in primary molars: a retro-spective study. Pediatr Dent 2000;22:192–9.

54. Ibrevic H, Al-Jame Q. Ferric sulfate as pulpotomy agent in primary teeth: twenty-month clinical follow-up. J Clin Pediatr Dent 2000;24:269 –72.

55. Burnett S, Walker J. Comparison of ferric sulfate, formocresol, and a combination offerric sulfate/formocresol in primary tooth vital pulpotomies: a retrospective radio-graphic survey. J Dent Child 2002;69:44 – 8.

56. Markovic D, Zibojinovic V, Bucetic M. Evaluation of three pulpotomy medicaments inprimary teeth. Eur J Paediatr Dent 2005;6:133– 8.

57. Agamy HA, Bakry NS, Mounir MM, Avery DR. Comparison of mineral trioxide aggre-gate and formocresol as pulp-capping agents in pulpotomized primary teeth. PediatrDent 2004;26:302–9.

58. Naik S, Hegde AM. Mineral trioxide aggregate as a pulpotomy agent in primarymolars: an in vivo study. J Indian Soc Pedod Prev Dent 2005;23:13– 6.

59. Farsi N, Alamoudi N, Balto K, Mushayt A. Success of minerals trioxide aggregate inpulpotomized primary molars. J Clin Pediatr Dent 2005;29:307–11.

60. Vargas KG, Packam BS, Lowman D. Preliminary evaluation of sodium hypochlorite forpulpotomies in primary molars. Pediatr Dent 2006;28:511–7.

61. Nadin G, Goel BR, Yeung CA, Glenny AM. Pulp treatment for extensive decay inprimary teeth. Cochraine Database Syst Rev 2003;CD0033220.

62. Loh A, O’Hoy P, Tran X, et al. Evidence-based assessment: evaluation of the formo-cresol vs ferric sulfate primary molar pulpotomy. Pediatr Dent 2004;26:401–9.

63. Fuks AB, Papagiannoulis L. Pulpotomy in primary teeth: review of the literature accordingto standardized assessment criteria. Eur Arch Paediatr Dent 2006;7:64–71.

64. Curzon MJ, Toumba KJ. Restoration of primary teeth: criteria for assessment of theliterature. Eur Arch Paediatr Dent 2006;7:48 –52.

65. Peng L, Ye L, Tan H, Zhou X. Evaluation of the formocresol vs mineral trioxideaggregate primary molar pulpotomy: a meta-analysis. Oral Surg Oral Med Oral PatholOral Radiol Endod 2006;102:e40 – 4.

66. Deery C. Formocresol and ferric sulfate have similar success rates in primary molarpulpotomy: in carious primary molars does a pulpotomy performed with ferric

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sulphate, compared with formocresol, result in greater clinical/radiographicsuccess? Pediatr Dent 2004;26:401–9.

67. What is meta-analysis? Available at: http://www.evidence-based-medicine.co.uk. Ac-cessed February 27, 2008.

68. Egger M, Davey Smith G, Phillips AN. Meta-analysis: principles and procedures. BrMed J 1997;315:1533–7.

69. Norbert V. The challenge of meta-analysis: discussion, indication, and contraindica-tions for meta-analysis. J Clin Epidemiol 1955;48:5– 8.

70. Sutton AJ, Abrams KR, Johns DR. An illustrated guide to the methods of meta-analysis.J Eval Clin Pract 2001;7:135– 48.

71. Cuisia ZE, Musselman R, Schneider P, Dummet CJR. A study of mineral trioxideaggregate pulpotomies in primary molars (abstract). Pediatr Dent 2001;23:168.

72. Jabbarifar SE, Khadeni DD, Ghaseni DD. Success rates of formocresol pulpotomy vsmineral trioxide aggregate in human primary molar tooth. J Res Med Sci2004;6:55– 8.

73. Aktoren O, Gencay K. A two-year clinical-radiographic follow-up of the pulpotomiesin primary molars (abstract). J Dent Res 2000;79:543.

74. Papagiannoulis L. Clinical studies on ferric sulphate as a pulpotomy medicament inprimary teeth. Eur J Paediatr Dent 2002;3:126 –32.

75. Waterhouse PJ, Nunn JH, Whitworth JN. An investigation of the relative efficacy ofBuckley’s formocresol and calcium hydroxide in primary molars vital pulp therapy.Br Dent J 2000;188:32– 6.

76. Liu JF. Effects of Nd:YAG laser pulpotomy on human primary molars. J Endod2006;32:404 –7.

Pulp Symposium


Vital Pulp Therapy with New Materials: New Directionsand Treatment Perspectives—Permanent TeethDavid E. Witherspoon, BDS, MS

AbstractPulp necrosis in immature teeth subsequent to carieshas a major impact on long-term tooth retention. Theaim of vital pulp therapy is to maintain pulp viability byeliminating bacteria from the dentin-pulp complex andto establish an environment in which apexogenesis canoccur. A complicating factor in treating immature teethis the difficulty predicting the degree of pulpal damage.The ability of the clinician to manage the health of theremaining pulpal tissue during the procedure is para-mount. Currently, the best method appears to be theability to control pulpal hemorrhage by using sodiumhypochlorite. Mineral trioxide aggregate (MTA) cur-rently is the optimum material for use in vital pulptherapy. Compared with the traditional material ofcalcium hydroxide, it has superior long-term sealingability and stimulates a higher quality and greateramount of reparative dentin. In the medium-term clin-ical assessment, it has demonstrated a high successrate. Thus, MTA is a good substitute for calcium hy-droxide in vital pulp procedures. (J Endod 2008;34:S25-S28)

Key WordsApexogenesis, direct pulp cap, mineral trioxide aggre-gate, pulpotomy

Dental caries is one of the greatest challenges to the integrity of the developing tooth.It can result in irreversible pulpal damage, eventually causing necrosis of the pulpal

tissues and associated arrested development of the tooth root. Ultimately, abnormalroot development will impact the long-term prognosis for tooth retention (1– 4). Thus,the primary goal when treating immature permanent teeth should be to maintain pulpvitality so that apexogenesis can occur (5– 8). Direct pulp caps and pulpotomies inteeth with incomplete root formation promote normal development of the root com-plex. There are long-term prognostic advantages of this treatment outcome over apexi-fication treatment. The tooth structure formed is of a great quantity, and its compositionappears to have greater structural integrity (3). The result is that the fully developedtooth is more resistant to vertical root fractures (4).

The classic study by Kakehashi et al. (9, 10) eloquently established the role ofbacteria in pulpal health and necrosis. In a germ-free environment, the pulp demon-strated the ability to heal and deposit additional dentin material. In the presence ofbacteria, pulpal demise was inevitable. This fundamental premise is integral to thesuccess of all vital pulp procedures. Thus, the basic principle of vital pulpal treatmentcan be broken down into 2 broad phases. The initial phase involves removing thediseased and bacterially contaminated tissue. The second phase involves establishing anenvironment that will prevent any further and future bacterial contamination. The prin-cipal procedures aimed at maintaining pulpal vitality include direct pulp caps andpulpotomies. By removing the affected coronal pulp tissue and leaving the unaffectedradicular pulp tissue in situ, sealed from the oral environment, normal root develop-ment can take place.

Historically, a number of materials (11–13) have been advocated to induce nor-mal root development. To date, the material of choice has been calcium hydroxide(Ca(OH)2) (14 –20). Most recently, an alternative material, mineral trioxide ag-gregate (MTA), has become available for use in pulpal procedures. Several prop-erties are necessary when choosing a material to be used in vital pulp treatment. Theseinclude the ability of the material to kill bacteria, induce mineralization, and establisha tight bacterial seal. The ideal material for vital pulp treatment should be able to resistlong-term bacterial leakage and stimulate the remaining pulp tissue to return to ahealthy state, promoting the formation of dentin. The early data for MTA suggest that itis the optimum material for fulfilling these goals when vital pulp therapy is the treatmentof choice.

MTA’s Physical and Chemical PropertiesMTA is composed of tricalcium silicate, bismuth oxide, dicalcium silicate, trical-

cium aluminate, and calcium sulfate dihydrate. MTA might also contain up to 0.6%insoluble residue, including free crystalline silica. Other trace constituents might in-clude calcium oxide, free magnesium oxide, potassium, and sodium sulfate compounds(21). Hydration of the powder results in the formation of a finely crystalline gel of thehydrated forms of the components, with some Ca(OH)2 also being formed. This solid-ifies to a hard structure in less than 3 hours (22). It has a compressive strength equalto intermediate restorative material (IRM) and Super-EBA IRM but less than that ofamalgam. MTA has been shown to have an antibacterial effect on some of the facultativebacteria and no effect on strict anaerobic bacteria (23). This limited antibacterial effectis less than that demonstrated by Ca(OH)2 pastes. MTA’s ability to resist the futurepenetration of microorganisms appears to be high. In in vitro leakage studies (24, 25),MTA has resisted leakage predictably and repeatedly. MTA frequently performs better

Private practice, Plano, Texas.Address requests for reprints to Dr David Witherspoon at

[email protected] of Interest: David E. Witherspoon, BDS, MS, has

acted as a Workshop Coordinator for the annual session of theAmerican Association of Endodontists.0099-2399/$0 - see front matter



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JOE — Volume 34, Number 7S, July 2008 Vital Pulp Therapy with New Materials S25

than amalgam IRM or Super EBA (26 –30). Compared with compositeresins placed under ideal conditions, MTA’s leakage patterns are simi-lar (31, 32). Furthermore, the presence of blood has little impact on thedegree of leakage (29, 33). It is commercially available as ProRoot MTA(Dentsply Tulsa Dental, Tulsa, OK) and has been advocated for use invital pulp therapy (34 –38).

MineralizationMTA has demonstrated the ability to induce hard tissue formation

in pulpal tissues when used as either a direct pulp capping or pulpotomymaterial (34, 36, 39 – 45). MTA promotes rapid cell growth in vitro(46). Compared with Ca(OH)2, in animal studies, MTA consistentlyinduces the formation of dentin at a greater rate with a superior struc-tural integrity. It develops more complete dentin bridges and demon-strates an improved ability to maintain pulp tissue integrity (34, 39).Histologic evaluation in animal and human studies has shown that MTAstimulates reparative dentin formation, with thick dentinal bridging,minimal inflammation, and nominal hyperemia. The net result is thatvital pulp therapy with MTA produces negligible pulpal necrosis (34,41– 43, 47).

MTA also appears to induce the formation of a dentin bridge at afaster rate than Ca(OH)2 (48). In 1 case report (52) partial pulpoto-mies were conducted on 2 cases of dens evaginatus. After 6 months, theteeth were removed as part of planned orthodontic treatment. Histo-logic examination of these teeth showed an apparent continuous dentinbridge formation in both teeth, and the pulps were free of inflammation.The process by which MTA acts to induce dentin bridge formation is notknown. It has been theorized (49) that the tricalcium oxide in MTAreacts with tissue fluids to form Ca(OH)2, resulting in hard tissue for-mation in a similar manner to Ca(OH)2.

Clinical OutcomesThe initial response reported in case reports has been very positive

(50 –52). Several human clinical studies with MTA for direct pulp cap-ping and pulpotomies have recently been published.

Direct Pulp CappingThe clinical data available on MTA pulp capping of cariously ex-

posed permanent teeth are limited to 2 studies. Both of these studieshave reported a high rate of success, which ranges from 93%–98% (53,54). In 1 study (54), 53 teeth with carious exposures that had beendiagnosed with reversible pulpitis and normal periradicular tissue weretreated with MTA pulp caps. A total of 40 patients between 7 and 45 yearsold were treated. Briefly, the treatment consisted of caries removal withthe aid of an operating microscope and extensive use of caries detectordye. Pulpal bleeding was controlled with 5.25%– 6.00% NaOCl appliedfor up to 10 minutes. After hemostasis was achieved, the pulps werecapped with MTA, and the teeth were temporized with unbonded com-posite Photocore (Kuraray Co Ltd, Osaka, Japan) and a moistened cot-ton pellet placed directly over the MTA. The teeth were restored with abonded composite 5–10 days later. Forty-nine of the 53 teeth wereavailable for recall at the 1-year time frame, with an average recallperiod of 3.94 years.

The maximum period of observation was 9 years. During that time,98% of the cases presented a favorable outcome, with a normal radio-graphic appearance, no symptoms, and a normal response to coldtesting. In addition, of the 15 teeth in younger patients that were not fullyformed at the time of treatment, all subsequently demonstrated contin-ued normal apexogenesis to complete root formation (54). In the sec-ond study, a 93% clinical and radiographic success rate was reported atthe 24-month recall period. The study used a similar protocol to direct

pulp cap 30 young, permanent, cariously exposed asymptomatic teethwith MTA. All the teeth showed signs of vitality and absence of periapicalradiolucency, with evidence of continued root growth and no reportedsymptoms (53).

PulpotomyThe human clinical data available on MTA pulpotomies in cari-

ously exposed permanent teeth have reported high success rates, whichranged from 93%–100%. In a prospective clinical trial comparing suc-cess rates of partial pulpotomies with treated cariously exposed perma-nent molars by using Ca(OH)2 or MTA, there was no statistically signif-icant difference in the success rate between each group (Ca(OH)2 �91%, MTA � 93%). Fifty-one teeth in 34 patients were available forrecall. The patients ranged from 6.8 –13.3 years old, and the fol-low-up period was from 25.4 – 45.6 months, with an average of 34.8months (55).

When comparing MTA and Ca(OH)2 pulpotomies within the samepatient at the 12-month recall time frame, 2 of the 15 teeth in theCa(OH)2 group were considered failures, whereas none of the teethtreated with MTA failed (0 of 15 teeth). Calcific metamorphosis wasevident radiographically in 2 teeth treated with Ca(OH)2 and in 4 teethtreated with MTA (56).

The use of gray MTA for partial pulpotomy in cariously exposedyoung permanent first molars diagnosed with reversible pulpitis andnormal periradicular tissue has resulted in a very high success rate.Exposed pulp tissue was removed with a diamond bur, and after hemo-stasis, 2– 4 mm of gray MTA was placed against the fresh wound andthen covered with a layer of glass ionomer cement. The teeth wererestored with amalgam or stainless steel crowns. At the 24-month recallperiod, 22 of 28 teeth showed no signs of clinical or radiographicfailure and responded within normal limits to pulp vitality tests. Al-though 6 of 28 teeth did not respond to vitality testing at the final follow-up, the radiographic appearance was within normal limits, and the teethwere asymptomatic. The patients’ ages ranged from 7.2–13.1 years,with an average age of 10 years (57).

In a case series outcomes report that used MTA pulpotomies totreat cariously exposed immature permanent teeth (first or second mo-lars) that had been diagnosed with irreversible pulpitis, a success rate of92% was reported (58). The key factor in deciding whether to completea pulpotomy as opposed to a pulpectomy was the ability to controlpulpal hemorrhage. In cases in which pulpal hemostasis could beachieved with NaOCl, a pulpotomy was completed. The patients’ agesranged from 7–15 years, with an average age of 10 years. The recallperiod ranged from 6 –53 months, with an average recall period of 21months. The single tooth that required nonsurgical root canal treatmenthad completed normal root development before requiring nonsurgicalroot canal treatment.

TechniqueWith the vital pulp therapy technique, the patient is anesthetized

with a standard local anesthetic protocol. In all cases, a rubber dam isused to isolate the tooth being treated. The affected enamel is removedby using a high-speed bur with copious irrigation. The gross caries canbe removed with either a sharp spoon excavator or a large, round,slow-speed tungsten carbide bur. As the pulp is approached, the cavityis flushed with NaOCl to decrease the bacterial load. The remainingaffected tissue is removed by using a coarse, high-speed diamond burwith copious irrigation. In the case of a pulpotomy, the pulp is removedto a level where adequate hemostasis can be achieved. Hemostasis isachieved by irrigating with 6% sodium hypochlorite (59) for up to 10minutes. Care should be taken to avoid the application of pressure to the

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S26 Witherspoon JOE — Volume 34, Number 7S, July 2008

pulp. Having achieved hemostasis, a layer of MTA should be placed andmixed according to the manufacturer’s recommendations over the ex-posed pulpal tissue. The thickness of the material should be approxi-mately 2 mm. Once the MTA is in place, a small amount of flowablecompomer (or an equivalent light-cured resin or glass ionomer liner)should be applied to cover the MTA material. The remainder of thecavity can then be etched, bonded, and restored (Fig. 1).

ConclusionThe major difficulty in treating permanent immature teeth is the

ability to predictably diagnose the state of pulpal health and, therefore,the ability of predicting it to heal. The current tests available to theclinician make it difficult to accurately predict the degree of pulpaldegeneration before commencing treatment. Therefore, the clinician’sability to assess the health of the remaining pulpal tissue during theprocedure is paramount. Currently, the best method appears to be theability to control pulpal hemorrhage with NaOCl.

The current data available on the use of MTA in vital pulp therapyindicate that it is the optimum material and better than the traditionallyused material Ca(OH)2. It has a greater long-term sealing ability andstimulates a high quality and a great amount of reparative dentin. Inclinical outcomes evaluation, it has demonstrated a high successrate. MTA is, thus, a good substitute for Ca(OH)2 in vital pulp pro-cedures.

References1. Robertson A, Andreasen FM, Andreasen JO, Noren JG. Long-term prognosis of crown-

fractured permanent incisors: the effect of stage of root development and associatedluxation injury. Int J Paediatr Dent 2000;10:191–9.

2. Rabie G, Trope M, Tronstad L. Strengthening of immature teeth during long-termendodontic therapy. Endod Dent Traumatol 1986;2:43–7.


4. Cvek M. Prognosis of luxated nonvital maxillary incisors treated with calcium hy-droxide and filled with gutta-percha: a retrospective clinical study. Endod DentTraumatol 1992;8:45–55.

5. Love RM. Effects of dental trauma on the pulp. Pract Periodontics Aesthet Dent1997;9:427–36, 38 (quiz).

6. Shabahang S, Torabinejad M. Treatment of teeth with open apices using mineraltrioxide aggregate. Pract Periodontics Aesthet Dent 2000;12:315–20, 22 (quiz).

7. Webber RT. Apexogenesis versus apexification. Dent Clin North Am 1984;28:669 –97.

8. Massler M. Preventive endodontics: vital pulp therapy. Dent Clin North Am1967;Nov:663–73.

9. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dentalpulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol1965;20:340 –9.

10. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dentalpulps in germ-free and conventional laboratory rats. J South Calif Dent Assoc1966;34:449 –51.

11. Horsted-Bindslev P, Vilkinis V, Sidlauskas A. Direct capping of human pulps with adentin bonding system or with calcium hydroxide cement. Oral Surg Oral Med OralPathol Oral Radiol Endod 2003;96:591– 600.

12. Trope M, McDougal R, Levin L, May KN Jr, Swift EJ Jr. Capping the inflamed pulpunder different clinical conditions. J Esthet Restor Dent 2002;14:349 –57.

13. Kiba H, Hayakawa T, Nakanuma K, Yamazaki M, Yamamoto H. Pulpal reactions to twoexperimental bonding systems for pulp capping procedures. J Oral Sci2000;42:69 –74.

14. Ulmansky M, Sela J, Langer M, Yaari A. Response of pulpotomy wounds in normalhuman teeth to successively applied Ledermix and Calxyl. Arch Oral Biol1971;16:1393– 8.

15. Schroder U, Granath LE. Scanning electron microscopy of hard tissue barrier follow-ing experimental pulpotomy of intact human teeth and capping with calcium hydrox-ide. Odontol Revy 1972;23:211–20.

16. Schroder U. Evaluation of healing following experimental pulpotomy of intact humanteeth and capping with calcium hydroxide. Odontol Revy 1972;23:329 – 40.

17. Holland R, de Souza V, de Mello W, Nery MJ, Bernabe PF, Otoboni Filho JA. Healingprocess after pulpotomy and covering with calcium hydroxide, Dycal, or MPC: his-tological study in dog teeth. Rev Fac Odontol Aracatuba 1978;7:185–91.

18. Holland R, de Souza V, de Mello W, Nery MJ, Bernabe PF, Otoboni Filho JA. Perme-ability of the hard tissue bridge formed after pulpotomy with calcium hydroxide: ahistologic study. J Am Dent Assoc 1979;99:472–5.

19. Stanley HR. Criteria for standardizing and increasing credibility of direct pulp cap-ping studies. Am J Dent 1998;11(special issue):S17–34.

20. Haskell EW, Stanley HR, Chellemi J, Stringfellow H. Direct pulp capping treatment: along-term follow-up. J Am Dent Assoc 1978;97:607–12.

21. Dentsply, Tulsa-Dental. Material safety data sheet: ProRoot MTA root canal repairmaterial. Tulsa, OK: Dentsply, 2002:1–2.

22. Torabinejad M, Hong CU, McDonald F, Pitt Ford TR. Physical and chemical propertiesof a new root-end filling material. J Endod 1995;21:349 –53.

23. Torabinejad M, Hong CU, Pitt Ford TR, Kettering JD. Antibacterial effects of some rootend filling materials. J Endod 1995;21:403– 6.

24. Wu MK, Kontakiotis EG, Wesselink PR. Long-term seal provided by some root-endfilling materials. J Endod 1998;24:557– 60.

25. Roy CO, Jeansonne BG, Gerrets TF. Effect of an acid environment on leakage ofroot-end filling materials. J Endod 2001;27:7– 8.

26. Torabinejad M, Rastegar AF, Kettering JD, Pitt Ford TR. Bacterial leakage of mineraltrioxide aggregate as a root-end filling material. J Endod 1995;21:109 –12.

27. Fischer EJ, Arens DE, Miller CH. Bacterial leakage of mineral trioxide aggregate ascompared with zinc-free amalgam, intermediate restorative material, and Super-EBAas a root-end filling material. J Endod 1998;24:176 –9.

28. Lee SJ, Monsef M, Torabinejad M. Sealing ability of a mineral trioxide aggregate forrepair of lateral root perforations. J Endod 1993;19:541– 4.

29. Martell B, Chandler NP. Electrical and dye leakage comparison of three root-endrestorative materials. Quintessence Int 2002;33:30 – 4.

30. Tang HM, Torabinejad M, Kettering JD. Leakage evaluation of root end filling mate-rials using endotoxin. J Endod 2002;28:5–7.

31. Adamo HL, Buruiana R, Schertzer L, Boylan RJ. A comparison of MTA, Super-EBA,composite, and amalgam as root-end filling materials using a bacterial microleakagemodel. Int Endod J 1999;32:197–203.

Figure 1. (A) Preoperative radiograph of a symptomatic cariously exposedmandibular second premolar. (B) Postoperative radiograph showing an MTApulpotomy completed and restored with bonded composite resin. (C) Recall at2.7 years showing continued root formation (apexogenesis). The tooth re-sponds within normal limits to pulp tests. (D) Recall at 3.4 years showing thetooth continuing to respond within normal limits to pulp tests.

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32. Fogel HM, Peikoff MD. Microleakage of root-end filling materials. J Endod2001;27:456 – 8.

33. Torabinejad M, Higa RK, McKendry DJ, Pitt Ford TR. Dye leakage of four root endfilling materials: effects of blood contamination. J Endod 1994;20:159 – 63.

34. Pitt Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP. Using mineraltrioxide aggregate as a pulp-capping material. J Am Dent Assoc 1996;127:1491– 4.

35. Torabinejad M, Chivian N. Clinical applications of mineral trioxide aggregate. J Endod1999;25:197–205.

36. Andelin WE, Shabahang S, Wright K, Torabinejad M. Identification of hard tissue afterexperimental pulp capping using dentin sialoprotein (DSP) as a marker. J Endod2003;29:646 –50.

37. Bakland LK. Management of traumatically injured pulps in immature teeth usingMTA. J Calif Dent Assoc 2000;28:855– 8.

38. Schmitt D, Lee J, Bogen G. Multifaceted use of ProRoot MTA root canal repair mate-rial. Pediatr Dent 2001;23:326 –30.

39. Faraco IM Jr, Holland R. Response of the pulp of dogs to capping with mineraltrioxide aggregate or a calcium hydroxide cement. Dent Traumatol 2001;17:163– 6.

40. Holland R, de Souza V, Murata SS, et al. Healing process of dog dental pulp afterpulpotomy and pulp covering with mineral trioxide aggregate or Portland cement.Braz Dent J 2001;12:109 –13.

41. Dominguez MS, Witherspoon DE, Gutmann JL, Opperman LA. Histological and scan-ning electron microscopy assessment of various vital pulp-therapy materials. J Endod2003;29:324 –33.

42. Aeinehchi M, Eslami B, Ghanbariha M, Saffar AS. Mineral trioxide aggregate (MTA)and calcium hydroxide as pulp-capping agents in human teeth: a preliminary report.Int Endod J 2003;36:225–31.

43. Tziafas D, Pantelidou O, Alvanou A, Belibasakis G, Papadimitriou S. The dentinogeniceffect of mineral trioxide aggregate (MTA) in short-term capping experiments. IntEndod J 2002;35:245–54.

44. Parirokh M, Asgary S, Eghbal MJ, et al. A comparative study of white and grey mineraltrioxide aggregate as pulp capping agents in dog’s teeth. Dent Traumatol2005;21:150 – 4.

45. Iwamoto CE, Adachi E, Pameijer CH, Barnes D, Romberg EE, Jefferies S. Clinical andhistological evaluation of white ProRoot MTA in direct pulp capping. Am J Dent2006;19:85–90.

46. Mitchell PJ, Pitt Ford TR, Torabinejad M, McDonald F. Osteoblast biocompatibility ofmineral trioxide aggregate. Biomaterials 1999;20:167–73.

47. Chacko V, Kurikose S. Human pulpal response to mineral trioxide aggregate (MTA):a histologic study. J Clin Pediatr Dent 2006;30:203–9.

48. Junn DJ, McMillan P, Bakland L, Torabainejad M. Quantitative assessment of dentinbridge formation following pulp-capping with mineral trioxide aggregate (MTA)(abstract). J Endod 1998;24:278.

49. Holland R, de Souza V, Nery MJ, Otoboni Filho JA, Bernabe PF, Dezan Junior E.Reaction of rat connective tissue to implanted dentin tubes filled with mineral trioxideaggregate or calcium hydroxide. J Endod 1999;25:161– 6.

50. Karabucak B, Li D, Lim J, Iqbal M. Vital pulp therapy with mineral trioxide aggregate.Dent Traumatol 2005;21:240 –3.

51. Patel R, Cohenca N. Maturogenesis of a cariously exposed immature permanent toothusing MTA for direct pulp capping: a case report. Dent Traumatol 2006;22:328 –33.

52. Koh ET, Ford TR, Kariyawasam SP, Chen NN, Torabinejad M. Prophylactic treatmentof dens evaginatus using mineral trioxide aggregate. J Endod 2001;27:540 –2.

53. Farsi N, Alamoudi N, Balto K, Al Mushayt A. Clinical assessment of mineral trioxideaggregate (MTA) as direct pulp capping in young permanent teeth. J Clin Pediatr Dent2006;31:72– 6.

54. Bogen G. Direct pulp capping with mineral trioxide aggregate: an observational study.J Am Dent Assoc 2008;139:305–15.

55. Qudeimat MA, Barrieshi-Nusair KM, Owais AI. Calcium hydroxide vs mineral trioxideaggregates for partial pulpotomy of permanent molars with deep caries. Eur ArchPaediatr Dent 2007;8:99 –104.

56. El-Meligy OA, Avery DR. Comparison of mineral trioxide aggregate and calciumhydroxide as pulpotomy agents in young permanent teeth (apexogenesis). PediatrDent 2006;28:399 – 404.

57. Barrieshi-Nusair KM, Qudeimat MA. A prospective clinical study of mineral trioxideaggregate for partial pulpotomy in cariously exposed permanent teeth. J Endod2006;32:731–5.

58. Witherspoon DE, Small JC, Harris GZ. Mineral trioxide aggregate pulpotomies: a caseseries outcomes assessment. J Am Dent Assoc 2006;137:610 – 8.

59. Hafez AA, Cox CF, Tarim B, Otsuki M, Akimoto N. An in vivo evaluation of hemorrhagecontrol using sodium hypochlorite and direct capping with a one- or two-componentadhesive system in exposed nonhuman primate pulps. Quintessence Int 2002;33:261–72.

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Indirect Pulp Therapy and Stepwise ExcavationLars Bjørndal, DDS, PhD

AbstractVarious treatment concepts have been suggested tosolve the deep carious lesion dilemma. Recent system-atic reviews are presented. Their conclusions are basedon very few studies, and the main message is thatoptimal randomized clinical studies are lacking. Obser-vational studies on indirect pulp treatment and step-wise excavation demonstrate that these treatmentsavoid pulp exposures, but it cannot be said whichapproach is best. A less invasive modified stepwiseexcavation approach is described, focusing on changingan active lesion into an arrested lesion even withoutperforming an excavation close to the pulp. In Denmarkand Sweden a randomized clinical multi-center trial iscurrently taking place, the Caries and Pulp (CAP) trial.This trial is investigating the effects of stepwise exca-vation over 2 visits versus 1 complete excavation ofdeep caries in permanent teeth. Guidelines for treat-ment are presented. (J Endod 2008;34:S29-S33)

Key WordsCaries, dentin, indirect pulp treatment, pulp, random-ized clinical trial, stepwise excavation, tertiary dentin

Introducing Thoughts about Level of Evidence in Clinical ResearchA demanding trend in clinical research is to perform a randomized clinical trial

(RCT) to compare 2 interventions. Why is RCT so important, or in particular therandomization? The level of evidence is the short answer to that question. Expert opin-ion is allocated to the lowest level of evidence, with the next level being observationalstudies. At the top of the hierarchy is the systematic review of high-quality RCTs. A moreextended answer deals with the largest problem in studies that are nonrandomized,which is that of confounding variables. Many factors cannot be controlled for if a simplecomparison is made between 2 studies in which the same treatment has been provided.The distribution of prognostic factors might differ between the 2 studies. Are the 2studies, in fact, treating the very same stage of diseases? With regard to caries, how deepare the lesions? Finally, we cannot exclude the psychological phenomenon that inves-tigators tend to see what they want to see. The perceived effect might in reality differbetween the 2 studies.

There is a great deal of difference between RCTs and observational studies, but thisdoes not mean that the thousands of clinical studies that have been carried out with anon-RCT design do not indicate relevance, but they simply do not have the highest levelof evidence.

The following is a list of factors that characterize a high-quality RCT:

1. the presence of well-defined inclusion and exclusion criteria;2. prognostic factors are equally distributed between the 2 interventions that are

going to be compared;3. the number of treatments needed to show a difference between control and

experimental groups is calculated;4. adequate allocation sequences: for example, the randomization of patients to

control or experimental groups is generated by a computer;5. adequate allocation concealment: the randomization is carried out with a central

independent unit;6. follow-up examination is done by an investigator(s) who is blinded as to the

patient’s group assignment;7. ideally, the RCT should be carried out in a number of trial centers.

The Latest Systematic Reviews from the Cochrane CollaborationRegarding Caries Treatment and the Pulp

The Cochrane Collaboration carries out systematic reviews of high-quality clinical stud-ies. The recent reviews of caries and pulp treatments all indicate the lack of RCTs (1, 2). TheCochrane Collaboration has found fewer than 10 studies that could be compared, and theyare not all high-quality RCTs.

Within the concept of maintaining pulp vitality, treatment modalities that includedindirect pulp treatment (IPT) showed no differences in symptoms at 12 months amongstudies using Life, Dycal, and Cavitec formulations of calcium hydroxide (2).

In relation to partial caries removal, the following points were addressed in thereview (1):

1. Partial caries removal in symptomless primary or permanent teeth reduces therisk of pulpal exposure;

2. No pulpal symptoms were found;3. Partial caries removal appeared preferable in deep lesions to reduce the risk of

carious exposure of the pulp;

From the Department of Cariology and Endodontics,School of Dentistry, Faculty of Health Sciences, University ofCopenhagen, Copenhagen, Denmark.

Address requests for reprints to Dr Bjørndal at [email protected].

Conflict of Interest: Lars Bjørndal, DDS, PhD, is a GrantRecipient from the Danish Agency for Science Technology andInnovation.0099-2399/$0 - see front matter



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JOE — Volume 34, Number 7S, July 2008 Indirect Pulp Therapy and Stepwise Excavation S29

4. There is insufficient evidence to show whether it is necessary tore-enter and excavate further in the stepwise excavation tech-nique, but studies that did not re-enter reported no adverseconsequences.

Let us add some comments, which in the future might bring theseconclusions further up the hierarchy of evidence. One problem hasbeen the definition of the penetration depth of the deep caries lesion.This point has in many studies been defined as a lesion in which onewould expect a pulpal exposure if all caries was removed. Among the 4included studies on which the above conclusions are based, the lesionsdiffered between deep lesions and those extending to half the thicknessof the dentin. In 2 of the studies, a stepwise excavation approach wasused with lesions defined as deep, whereas the other 2 studies did notre-enter the lesion. The problem in comparing these studies is con-founding factors. One of the studies treated less progressed lesions,which might be important when trying to compare the 2 interventions.

We need high-quality RCTs to compare IPT and stepwise excava-tion. I will return to this later.

How Deep Is a “Deep” Caries Lesion?The definition of deep caries lesions points toward the potential

exposure of the pulp (3). When do clinicians expect that a potentialpulp exposure is close? In a practice-based observational study, generaldentists were asked to judge the penetration depth of caries lesions thatwould pose a risk for pulpal exposure (4). The majority of dentistsselected lesions that penetrated to within three fourths of the entiredentin thickness or more as evaluated on x-rays. This judgment wasmade in one case in which only half of the dentin was demineralized,indicating that this definition varies substantially among practitioners.

Let us adopt the same clinical concern for potential exposures asdid the majority of these general practitioners. A deep caries lesion ispresent when the penetration depth is in the range of three fourths of theentire thickness of the dentin or more when evaluated on an x-ray.

The Biologic DilemmaOn the first day of this symposium, we discussed the understanding

of caries, and that the treatment of deep caries lesions has been placedin what one could call “no mans land,” with different schools of opin-ions as classically given by Tomes (5) and Black (6). Another aspect isthat we do not have any reliable or accurate clinical diagnostic devicefor monitoring the degree of pulpal inflammation. The case selection fora given treatment, whether or not we want to avoid an exposure of thepulp, is still based on indirect diagnostic procedures. We might try todivide a few clinical stages of vital pulp problems, depending on theresults from our clinical as well as paraclinical diagnostic procedures,as described in detail by Reit et al. (7). The diagnostic data should becollected from the following 3 areas: (i) the patient’s description ofsubjective symptoms, (ii) pulp sensibility testing, and (iii) paraclinicalexaminations (radiographs for exclusion of apical pathosis).

Attempts to divide degrees of pulp pathology seem ambitious, be-cause we do not always know in what direction the pulpal inflammationwill turn. It has not been possible to devise an overall applied classifi-cation system on this issue. For some practitioners, the clinical diagno-sis of the pulp is centered on subjective symptomatic factors, ie, symp-tomatic or nonsymptomatic pulpitis (8), whereas for others the use ofreversible and irreversible pulpitis is applied (9). Within the latter di-agnosticdichotomy, the treatments are guided toward either invasivepulp therapy or procedures aiming to maintain the pulp integrity. Thus,the words irreversible and reversible cannot solely be interpreted as thegold standard expression for the actual state of the pulp, but rather theyrepresent our best clinical judgment.

The Dentist Must Handle the Biologic Dilemma!The clinical use of the irreversible pulpitis diagnosis as well as

symptomatic pulpitis is essentially the same; the tooth will be managedwith an invasive pulp treatment (9). However, the deep carious lesionmight also be a potential reversible pulpitis case, with confirmed pulpalsensibility but with no objective signs of apical pathology or subjectivesymptoms before start of the treatment. Even though the absence ofclinical symptoms is not a sign of absence of pulp pathology, this ap-proach provides one more chance to maintain the pulp’s integrity, untilthe opposite is proved. An important point after treatment of such casesmust be the maintenance of pulp sensibility, because the finding of “noclinical symptoms” could be the result of a silently developing pulpnecrosis.

A Brief Historical Focus on Excavations Methods inAsymptomatic Deep Caries Lesions

Many pulps have probably been exposed through the years on thebasis of the concept that deep caries lesions are always associated withinflammation, and diagnoses such as asymptomatic pulpitis or chronicpulpitis have been made. Various excavation methods have been pro-posed, such as IPT (10) and the two-stage excavation procedure orstepwise excavation (11). In recent articles and reviews the expression“partial excavation” (1) has emerged to refer to various treatment mo-dalities, but in reality the term has not led to consensus, because it canmean anything from almost no excavation to excavation very close to thepulp. The differences between the 2 methods mentioned above are thatthe IPT procedure involves almost complete removal of the affecteddentin, leaving a thin layer of demineralized dentin. Re-entry is notattempted. In contrast, the stepwise excavation technique involves re-entry at varying intervals. What did these early clinical articles prescribein terms of clinical procedure?

One of the earliest articles describing a step-by-step approach is bySowden (12). Carious tissue was removed, and a 1-mm layer of calciumhydroxide was placed followed by a temporary restoration. No finalexcavation was performed within the first visit. Re-entry and final exca-vation were then made after 2–3 weeks.

A more rigorous approach was addressed in the article by Mag-nusson and Sundell (11), who emphasized that a thin soft layer of dentinshould remain on the pulpal wall. The authors did not describe in detailwhat was meant by a thin layer. They most likely excavated as close aspossible to the pulp, leaving a thin layer of residual caries. Residualcaries, as defined by Kerhove et al. (10), means that if you apply addi-tional pressure to the dentin with the excavator, the pulp will be ex-posed. Magnusson and Sundell (11) placed a zinc oxide– eugenol ce-ment temporary restoration and performed the final excavation after4 – 6 weeks. This stepwise excavation method has been a very commonand widespread approach within the Nordic countries. In 1962, Lawand Lewis (13) accessed all areas of carious dentin and placed calciumhydroxide and an amalgam restoration. Re-entry was made after 6months.

Eidelman et al. (14) provided details of the excavation proce-dures. It is stated that all undermining enamel is removed to gain moreeasy access to the carious dentin along the enamel-dentin junction. Atthe pulpal wall approximately 1 mm of carious dentin was left behind.The tooth was re-entered after 1 year, and the final excavation wasperformed.

For reasons discussed earlier, we cannot make detailed compar-isons among these older studies, because each represents its own de-cade, and there is a great deal of variation among them. For example, inthe study by Magnusson and Sundell (11), primary teeth were treated,and no follow-up examination was done after treatment was completed.

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Note that it is also difficult to determine whether there are anydifferences between the classic IPT and the first excavation step asperformed in the study by Magnusson and Sundell (11). Thus, thepotential risk of creating pulpal exposures following either IPT or dur-ing the first step of stepwise excavation might very well be the same.

Observational Data about Indirect Pulp TreatmentIn a retrospective study AL-Zayer et al. (15) found that IPT in

primary posterior teeth is a successful technique and should be consid-ered as an alternative pulp therapy. Recently, Gruythuysen et al. (16)also reported that the IPT technique produces clinical success. Con-cerning the more detailed treatment procedures, the Cochrane reviewindicated that variation in base materials did not produce any differ-ences (2). Also, Marchi et al. (17) concluded that IPT in primary teetharrests the progression of the underlying caries, regardless of the ma-terial used as a liner.

Use the Knowledge from Caries Pathology to Designan Excavation Approach

The optimal focus on avoiding a pulpal exposure and using cariespathology might be demonstrated by the concept of a less invasive ormodified stepwise excavation (Fig. 1) (18, 19). The primary aim of the

first excavation is to change the caries environment and not to remove asmuch carious dentin, eventually reaching the residual level close to thedentin-pulp interface. Microbiologic and clinical studies have shownthat it is possible to decrease the number of bacteria and arrest thecaries process during a treatment interval (19, 20). The active, soft,yellowish demineralized dentin becomes a darker, harder, and drierdemineralized dentin, resembling a slowly progressing lesion. Moredetailed microbiologic observations also indicate that during a treat-ment interval the flora becomes a type associated with slow lesionprogress in root caries (21). These findings have gained additionalsupport (22). Whether the presence of such flora can remain “inactive”beneath a permanent restoration in a deep cavity needs further investi-gation.

This aspect of using our knowledge of caries pathology as anintegrated part of caries removal is also reinforced in a new textbookchapter (23).

Is A Two-step Excavation Necessary?As shown from a recent survey, 18% of respondents would par-

tially remove caries in a deep lesion in which one would expect thatcomplete caries removal would lead to pulpal exposure (24). I inter-pret this technique as the IPT with no re-entry. In the United States IPT

Figure 1. Diagrams demonstrating the less invasive stepwise excavation procedure. A closed lesion environment before and after first excavation (a, b) followed bya calcium hydroxide– containing base material and a provisional restoration. During the treatment interval the retained demineralized dentin has clinically changedinto signs of slow lesion progress, evidenced by a darker demineralized dentin (c, d). After final excavation (e) the permanent restoration is made (f). Red zonesindicate plaque. Reprinted with permission from Blackwell Munksgaard from Bjørndal L. Dentin and pulp reactions to caries and operative treatment: biologicalvariables affecting treatment outcome. Endodontic Topics 2002;2:10 –23. (27)

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has been carried out for years, whereas we in the Scandinavian coun-tries traditionally have applied a stepwise excavation approach. It isdifficult to state which treatment approach is better, because no high-quality RCTs have yet been performed to give us the answer.

The clinician’s intention is to avoid a pulpal exposure on the basisof the best possible indications. The main concern is that when exca-vating to a level close to the pulp, a number of pulpal complicationsmight arise, as indicated within the various stepwise excavation ap-proaches. Clinically, the changes in dentin appearance during the ex-cavation provide the clinician with information regarding the changes incaries activity. This is also true in cases in which the changes in color ofthe carious dentin are not as clear. The final excavation is safer, becauseit is easier to remove the remaining dry carious dentin.

The final step of stepwise excavation is 2-fold: (1) to assess thetooth’s reaction and (2) to remove the slowly progressing lesion inslightly infected discolored demineralized dentin before carrying outthe final restoration.

A Two-step Approach Might Be the First Way ofChanging Clinical Habits

The vast majority of respondents to the aforementioned surveyselected an invasive approach in relation to the deep caries case be-cause they presumably did not believe in leaving carious dentin behind(24). If the operator leaves infected dentin, it might stimulate oblitera-tion of the root canals, making future endodontic treatment more diffi-cult. It is important to say that such a hypothesis is relevant, but it has notbeen proved. In reality, this would favor a second visit. Remember thesecond aim, which is to remove the slowly progressing caries in slightlyinfected discolored demineralized dentin before carrying out the finalrestoration.

However, it is not easy to change a clinical habit from one ofremoving all carious dentin to one of leaving caries permanently. Oneway to accomplish this would be to experience the strategy of “changingthe local caries environment” by performing a 2-step procedure nexttime a deep caries lesion presents in your practice.

A High-quality RCT Concerning Deep Caries Treatment:The Caries and Pulp (CAP) Trial

The aim of the CAP trial has been to investigate the beneficial andharmful effects of stepwise excavation of symptomatic and asymptom-atic permanent teeth during 2 visits versus complete excavation of deepcaries in 1 visit. The CAP trial is being performed as a multi-center RCT,and the status of inclusion has recently been reported, which means thatthe enrollment of patients has been discontinued, and the results areabout to be analyzed (25). Preliminary data on the outcome pulp ex-posure favor the use of stepwise excavation.

Clinical Guidelines Based on an Observational Studyand a High-quality RCT

Observational studies from dental practice environments havedemonstrated the effectiveness of treating deep carious lesions byusing a less invasive or modified stepwise excavation. Long-termrecall (3.5– 4.5 years) has demonstrated a high success rate (92%),indicating that the method can be carried out in clinical practice(26). The placement of high-quality temporary and final restorativematerials must be stressed, because failures are most often associ-ated with inadequate restorations (4). Therefore, a 2-step excava-tion procedure will add to the cost of the treatment. Because of thepossibility of asymptomatic development of irreversible pulp degen-eration over time, follow-up examinations are required with regardto pulp sensibility and apical conditions. Because readers are al-

ready familiar with the guidelines of the IPT, the following presentsthe stepwise excavation technique (27):

1. Deep lesion considered likely to result in pulp exposure if treatedby a single and terminal excavation. Evaluated by x-ray, the den-tinal lesion involves three fourths or more of the dentin thickness.

2. No history of pretreatment symptoms such as spontaneous painand provoked pulpal pain. However, mild to moderate pain onthermal stimulation is accepted.

3. Positive pulp sensibility tested by an electric pulp tester, thermalstimulation, or test cavity.

4. Pretreatment radiographs that rule out apical pathosis.5. Finish the peripheral excavation of the cavity followed by a central

excavation removing the outermost necrotic and infected demin-eralized dentin, in order that a provisional restoration can beproperly placed.

6. Do not excavate as closely as possible during the first step,thereby reducing the risk of pulp exposure.

7. Select a provisional restorative material on the basis of the lengthof the treatment interval, ranging between 6 and 8 months.

8. The final excavation is often less invasive than expected, as aresult of the altered dentinal changes gained during the treatmentinterval.

Recognize that the procedure appears very similar to the IPT,except for the less invasive first step. This requires the clinician todecide before reaching the pulp whether to perform a stepwiseexcavation approach before all carious dentin has been removed.Otherwise, the clinician will not promote local changes in the car-iogenic environment.

It Is Not Just a Matter of Selecting a Proper ClinicalTreatment Concept

We do not yet have noninvasive tools for the measurement of theseverity of pulpal inflammation. Thus, the discussion of reversible orirreversible development of pulpitis is controversial in relation to theactual state of the pulp. When treating the deep carious lesion, we areforced to make a choice on the basis of indirect diagnostic methods.Consequently, different schools of thought exist. Future high-qualityRCTs might reduce this problem. The understanding of clinical treat-ment concepts also includes knowledge of its limitations. The controland prevention of further pulpal and periapical damage in relation tothe restored tooth will, besides a sufficient restoration, include properoral hygiene procedures for the removal of cariogenic biofilms, whichtend to accumulate where the problem began—in the areas of therestored tooth surfaces. In addition, follow-up examinations are man-datory for the evaluation of pulp sensibility and the possible presence ofapical pathosis (28).

References1. Ricketts DNJ, Kidd EAM, Innes N, Clarkson J. Complete or ultraconservative removal

of decayed tissue in unfilled teeth. Cochrane Database Syst Rev 2006;3:CD003808.2. Miyashita H, Worthington HV, Qualtrough A, Plasschaert A. Pulp management for caries in

adults: maintaining pulp vitality. Cochrane Database Syst Rev 2007;2:CD004484.3. Fitzgerald M, Heys RJ. A clinical histological evaluation of conservative pulpal therapy

in human teeth. Oper Dent 1991;16:101–12.4. Bjørndal L, Thylstrup A. A practice-based study on stepwise excavation of deep

carious lesions in permanent teeth: a 1-year follow-up study. Community Dent OralEpidemiol 1998;26:122– 8.

5. Tomes J. A system of dental surgery. London: John Churchill, 1859:336.6. Black GV. A work on operative dentistry in two volumes, vol II. The technical proce-

dures in filling teeth. 2nd ed. Chicago: Medico-Dental Publishing Co, 1908.7. Reit C, Petersson K, Molven O. Diagnosis of pulpal and periapical disease. In: Ber-

genholtz G, Hørsted-Bindslev P, Reit C, eds. Textbook of endodontology. Oxford:Blackwell Munksgaard, 2003:9 –18.

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8. Tronstad L. Clinical endodontics. 2nd ed. Stuttgard: Thieme, 2003:81.9. Trope M, Sigurdsson A. Clinical manifestation and diagnosis. In: Ørstavik D, Pitt Ford

TR, eds. Essential endodontology: prevention and treatment of apical periodontitis.Oxford: Blackwell Sci. Ltd, 1998:157–78.

10. Kerkhove BC, Jr, Herman SC, Klein AI, McDonald RE. A clinical and television densitomet-ric evaluation of the indirect pulp capping technique. J Dent Child 1967;34:192–201.

11. Magnusson BO, Sundell SO. Stepwise excavation of deep carious lesions in primarymolars. J Int Assoc Dent Child 1977;8:36 – 40.

12. Sowden JR. A preliminary report on the recalcification of carious dentin. J Dent Child1956;23:187–8.

13. Law DB, Lewis TM. The effect of calcium hydroxide on deep carious dentin. Oral SurgOral Med Oral Path 1961;14:1130 –7.

14. Eidelman E, Finn SB, Koulourides T. Remineralization of carious dentin treated withcalcium hydroxide. J Child Dent 1965;32:218 –25.


16. Gruythuysen RJM, van Strijp AJP, Gunawan MIM, Ramdas M. Indirect pulp treatmentin primary and permanent teeth with deep carious lesions. Caries Res 2007;41:269.

17. Marchi JJ, de Araujo FB, Fröner AM, Straffon LH, Nör JE. Indirect pulp capping in theprimary dentition: a 4 year follow-up study. J Clin Pediat Dent 2006;31:68 –71.

18. Massler M. Treatment of profound caries to prevent pulpal damage. J Pedod 1978;2:99–105.19. Bjørndal L, Larsen T, Thylstrup A. A clinical and microbiological study of deep carious

lesions during stepwise excavation using long treatment intervals. Caries Res1997;31:411–7.

20. Pinto AS, de Araújo FB, Franzon R, et al. Clinical and microbiological effect ofcalcium hydroxide protection in indirect pulp capping in primary teeth. Am JDent 2006;19:382– 6.

21. Bjørndal L, Larsen T. Changes in the cultivable flora in deep carious lesions followinga stepwise excavation procedure. Caries Res 2000;34:502– 8.

22. Paddick JS, Brailsford SR, Kidd EAM, Beighton D. Phenotypic and genotypic selectionof microbiota surviving under dental restorations. Appl Environ Microbiol2005;71:2467–72.

23. Kidd EAM, Bjørndal L, Beighton D, Fejerskov O. Caries removal and the pulpo-dentinal complex. In: Fejerskov O, Kidd EAM, eds. Dental caries: the disease andits clinical management. 2nd ed. Oxford: Blackwell Munksgaard, 2008:367– 83.

24. Oen KT, Thompson VP, Vena D, et al. Attitudes and expectations of treating deepcaries: a PEARL network survey. Gen Dent 2007;55:197–203.

25. Bjørndal L, Bruun G, Markvart M, et al. The CAP-1 randomized trial: stepwise exca-vation versus one excavation - status of inclusion. Caries Res 2007;41:270.

26. Bjørndal L: Behanding af profunde carieslæsioner med gradvis ekskavering. En praksisbaseret undersøgelse (English summary). Tandlægebladet 1999;103:498–506.

27. Bjørndal L. Dentin and pulp reactions to caries and operative treatment: biologicalvariables affecting treatment outcome. Endodontic Topics 2002;2:10 –23.

28. Bjørndal L, Mjör IA. Dental caries: characteristics of lesions and pulpal reactions. In:Mjör IA, ed. Pulp-dentin biology in restorative dentistry. Chicago: Quintessence Pub-lishing Co, 2002:55–75.

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Indirect Pulp Capping and Primary Teeth: Is the PrimaryTooth Pulpotomy Out of Date?James A. Coll, DMD, MS

AbstractFormocresol pulpotomy (FP) in the United States ismost frequently used to treat asymptomatic caries nearthe pulp in primary teeth. Indirect pulp therapy (IPT) isalso indicated and has a significantly higher long-termsuccess. Pulpotomy is thought to be indicated for pri-mary teeth with carious pulp exposures, but researchshows the majority of such teeth are nonvital or ques-tionable for treatment with vital pulp therapy. IPT hasa significantly higher success in treating all primary firstmolars, but especially those with reversible pulpitiscompared with FP. The purpose of this article was toreview the dental literature and new research in vitalpulp therapy to determine the following: (1) Is a pul-potomy indicated for a true carious pulp exposure? (2)Is there a diagnostic method to reliably identify teeththat are candidates for vital pulp therapy? (3) Is primarytooth pulpotomy out of date, and should indirect pulptherapy replace pulpotomy? (J Endod 2008;34:S34-S39)

Key WordsIndirect pulp therapy, pulp exposure, pulpotomy

The guidelines of the American Academy of Pediatric Dentistry (AAPD) on pulptherapy for primary and young permanent teeth states that a pulpotomy is a proce-

dure in which the coronal pulp is amputated, and the remaining radicular pulp tissue istreated with a medicament or electrocautery to preserve the pulp’s health (1). Theguidelines state the objective of a pulpotomy is to keep the remaining pulp healthywithout adverse clinical signs or symptoms or radiographic evidence of internal orexternal root resorption. The AAPD guidelines further state that there is only one otherchoice for vital pulp therapy in primary teeth where caries approach the pulp. Thischoice is indirect pulp therapy (IPT), because the direct pulp cap in a primary tooth iscontraindicated for carious exposures (1). IPT is a procedure in which the cariesclosest to the pulp is left in place and covered with a biocompatible material, and thetooth is restored to prevent microleakage. The objectives of treatment are the same asfor a pulpotomy (1).

For deep caries in primary teeth, the indications for IPT and pulpotomy areidentical for reversible pulpitis or a normal pulp when the pulp is judged to be vital fromclinical and radiographic criteria (1). The difference occurs when the caries removalprocess results in a pulp exposure; a pulpotomy is then undertaken. IPT purposelyavoids an exposure by leaving the deepest decay in place. IPT is clearly not indicatedwhen the pulp is exposed by caries, but is pulpotomy indicated for a carious pulpexposure? For deep caries with possible radiographic exposures that are asymptomatic,which is the better choice of treatment, IPT or pulpotomy?

The purpose of this article was to review the dental literature and new research invital pulp therapy to determine the following: (1) Is a pulpotomy indicated for a truecarious pulp exposure? (2) Is there a diagnostic method to reliably identify teeth that arecandidates for vital pulp therapy? (3) Is primary tooth pulpotomy out of date, andshould IPT replace pulpotomy?

Is Pulpotomy Indicated for Carious Exposures?A primary tooth pulpotomy should be performed on a tooth judged to have a vital

pulp (1). After the coronal pulp is amputated, this leaves behind vital radicular pulptissue that has the potential for healing and repair in 3 general ways, according to Rodd(2). First, the remaining radicular pulp can be rendered inert, such as by using formo-cresol. It fixes or denatures the vital pulp so it is no longer pulp tissue in addition to itsbactericidal properties. Second, the radicular pulp might be preserved through mini-mal inflammatory insult by using a hemostatic agent such as ferric sulfate to form a clotbarrier to preserve the deeper remaining pulp tissue. The third pulpotomy mechanismencourages the radicular pulp to heal and form a dentin bridge by using calciumhydroxide or mineral trioxide aggregate (MTA).

What is the histologic and clinical research that can help dentists determine whichteeth with deep caries are vital and, thus, candidates for pulpotomy? Reeves and Stanley(3) found that as long as the advancing edge of the carious lesion was 1.1 mm from thepulp, no significant pathologic changes were evident in permanent teeth. Once thecaries approached within 0.5 mm of the pulp and the reparative dentin was involved,then significant pathologic changes were noted. Shovelton (4) examined permanentteeth and showed that as caries approximated 0.25– 0.3 mm of the pulp, hyperemia andpulpitis were seen.

Regarding the effect of pulp exposures on the pulp’s capacity to repair, Lin andLangland (5) showed that that when no pulp exposure occurred from caries, the pulp’srepair capacity was excellent. After a carious exposure, however, it was questionable

From the Department of Pediatric Dentistry, University ofMaryland Dental School, Baltimore, Maryland.

Address requests for reprints to Dr Coll at [email protected].

Conflict of Interest: James A. Coll, DMD, MS, is a paidconsultant to the Maryland State Dental Board in the reviewof dental charts of pediatric patients.0099-2399/$0 - see front matter



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S34 Coll JOE — Volume 34, Number 7S, July 2008

and unpredictable. They also found that in teeth with a history of pain,the pulp chamber would have an area of necrosis often extending intothe radicular pulp. Others have stated that the dentist risks displacinginfected dentin chips into the pulp when performing total excavation ofdeep carious lesions, thus increasing the risk of pulpal inflammatorybreakdown (6).

Stepwise caries removal in permanent teeth thought to have radio-graphic pulp exposures has been proposed as a method to minimizepulp exposures and preserve vitality (7, 8). Caries excavation is a 2-ap-pointment procedure. Initially, the lesion’s periphery is made caries-free, while the center of the caries is partially removed to leave moist,soft dentin over the pulp. Then, calcium hydroxide and a temporaryfilling are placed for 6 –12 months. The lesion is then re-entered, and allthe caries is removed. Bjorndal et al. (7) found no pulp exposures onre-entry in 31 permanent teeth by using stepwise caries removal. Leskellet al. (8) tested stepwise caries removal versus conventional in 127permanent teeth with a patient mean age of 10.2 years. After 8 –24

months, stepwise removal resulted in approximately 18% pulp expo-sure versus 40% for conventional caries removal.

Many of these permanent tooth findings likely apply to primaryteeth. Rodd (2) stated that carious primary and permanent teethshowed similar neural changes when mounting a pulpal defense to deepcaries. Rodd found that primary and permanent teeth have similar vas-cularity, except in the midcoronal region, and showed a similar degreeof vasodilatation and new vessel formation with caries progression.

Eidelman et al. (9) studied severely decayed primary incisors withno pulp pathology in nonrestorable teeth from 20- to 42-month-oldchildren. After fixation, caries was removed with a slow-speed roundbur. A sharp explorer was used to evaluate total caries removal andcheck for a pulp exposure. Teeth without pulp exposures and no totalnecrosis likely as a result of trauma were histologically diagnosed astreatable with vital pulp therapy in 23 of 26 cases (88%). By contrast, 16of 24 (67%) of the incisors judged to be nontreatable (total necrosis)or questionable (chronic partial pulpitis) for treatment with vital pulp

Figure 1. Example of using glass ionomer caries control to diagnose reversible pulpitis or food impaction in a mandibular first primary molar with a history of painto chewing sweets and solid foods for 2–3 weeks. (a) Preoperative view. (b) Preoperative radiograph. (c) View immediately after glass ionomer placement. (d) Twomonths after caries control. Pain stopped from day glass ionomer placed. No clinical or radiographic sign of irreversible pulpitis. (e) View of IPT with a glass ionomerbase. (f) Tooth 16 months after treatment without signs of pain or irreversible pulpitis clinically or on the radiograph.

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JOE — Volume 34, Number 7S, July 2008 Indirect Pulp Capping and Primary Teeth S35

therapy had a carious pulp exposure, leaving only 33% that were un-questionably vital. Dentists might think they can obtain a 90% level ofpulpotomy success in such a case. The simple mathematics of 33%(chance of finding a vital pulp) � 90% (chance of pulpotomy success),however, would equal a 30% chance of a cariously exposed tooth havinga successful pulpotomy. From these histologic and clinical findings, thefollowing conclusions can be drawn:

1. Primary tooth pulpotomy requires a vital radicular pulp, no mat-ter what form or type of pulpotomy procedure is used (1, 2).Teeth with a carious pulp exposure have a low likelihood of beingtotally vital (9) and are, thus, poor candidates for vital pulpotomy.

2. Stepwise caries removal will result in fewer pulp exposures thantotal caries removal performed in 1 visit (7, 8).

3. For teeth without carious pulp exposures, performing a pulpot-omy likely increases the chance of displacing infected dentinchips into the pulp and impairing the pulp’s repair capacity (5,6).

4. The pulp’s repair capacity is excellent when the carious lesionremains 1 mm or more away from the pulp (3).

Is There a Diagnostic Method to Identify Teeth withDeep Caries That Are Symptomless or Questionable,

Yet Are Candidates for Vital Pulp Therapy?Identifying those teeth with deep caries that are vital and treatable

with vital pulp therapy leads to this article’s second purpose, which wasto describe a new method to reliably diagnose these teeth. Initiallyplacing an intermediate, therapeutic, temporary restoration by usingglass ionomer caries control (GICC) for 1–3 months before startingpulp therapy has been shown to be an excellent method of diagnosingthe pulp’s vitality. No anesthesia is used to perform minimal cariesexcavation with spoon excavators or slow-speed round burs and is aform of alternative restorative treatment (ART) (10) or stepwise cariesremoval (7). This procedure takes less than 5 minutes and can be doneat the initial examination visit of a child presenting with multiple opencarious lesions.

GICC is indicated in cavitated carious lesions to diagnose theirvitality in teeth with signs and symptoms of reversible pulpitis or asymptomless tooth thought to have no pulpitis before instituting anypulp therapy (11). The technique involves minimally removing the su-perficial, nonpainful decay by using a slow-speed no. 4 or 6 round buror spoon excavation. A glass ionomer temporary filling is then placed byusing a material such as Fuji IX (GC America Inc, Alsip, IL), Ketac Molar(3M ESPE, St Paul, MN), Voco Ionofil Molar AC (Voco Gmbh, Cuxhaven,Germany), or a resin-modified glass ionomer. A matrix band does nothave to be used, but the intermediate therapeutic temporary restorationshould not be in occlusion. After 1–3 months of GICC, if the tooth hasbeen asymptomatic and shows no signs of irreversible pulpitis clinicallyor on a new radiograph, vital pulp therapy can be instituted by using IPTor pulpotomy (Fig. 1).

Numerous studies have reported on the biologic effects of a glassionomer temporary filling. Bonecker et al. (12) studied dentin samplesin 40 primary molars before and after ART excavation. The total bacte-rial count and mutans streptococci were significantly reduced from theexcavation process alone. Loyola-Rodriquez et al. (13) showed in vitrothat all glass ionomer liners had good antibacterial activity againstStreptococcus sobrinus and S. mutans associated with their fluoriderelease.

Wambier et al. (14) published an in vivo study of 32 primarymolars with open deep carious lesions. Radiographs and examinationsexcluded teeth with apical pathosis. Initially, carious dentin sampleswere taken, and then minimal caries excavation was performed fol-

lowed by a resin-modified glass ionomer temporary filling. After 30 and60 days of temporization, the second dentin samples showed that totalbacterial counts decreased significantly (P � .05), and all bacterialstrains had similar trends in both time periods. Scanning electron mi-croscopy inspection of dentin samples in the same time frames showeddentin reorganization and narrower dentin tubules. The authors be-lieved the results suggested that sealing the cavitated lesion with glassionomer contributes to remineralization. Only the outer carious layerneeds to be removed to accomplish this result. Oliveira et al. (15)reported on 32 permanent teeth after minimal caries excavation andtemporization for longer time periods. They concluded that total cariesremoval did not seem essential to stop caries progression.

Regarding the effect of glass ionomer on the subsequent vital pulptherapy, Vij et al. (11) reported that GICC temporization for 1–3 monthsincreased success of the subsequent vital pulp therapy from 79% to92%. Teeth temporized with zinc oxide– eugenol, however, had a suc-cess rate of 67%. They also reported a “drying out” effect of the moistcaries on re-entry after GICC similar to that reported by Bjorndal et al.(7) after 6 –7 months of stepwise caries removal.

Another recently completed study reported on GICC’s diagnosticsuccess in deeply cavitated carious lesions (16). A group of primarymolars had GICC after minimal caries excavation for a mean time of 3.5months. The GICC intermediate therapeutic temporary restoration hadto have remained intact without displacement for 1– 4 months. Anothergroup of primary molars had no GICC. Both groups had IPT or formo-cresol pulpotomy and were restored with an immediate steel crown theday of treatment and were followed for a mean time of more than 3years. Diagnostic success was based on the vital pulp therapy success, orthe tooth was successfully diagnosed with irreversible pulpitis after 1–3months of GICC. The GICC group showed a significant increase (P �.001) in the subsequent vital pulp therapy success (98%) versus thenon-GICC group’s vital pulp therapy success (75%). There was a sub-group of 18 teeth that presented with pain and/or a questionable diag-nosis of their vitality. All received GICC initially for 1– 4 months todiagnose the tooth’s vitality. The GICC produced the correct diagnosisfor all the teeth in that 7 molars returned with signs of irreversiblepulpitis and were extracted. For the other 11, however, the pain wasdiagnosed as reversible, and all were treated with vital pulp therapysuccessfully.

From these microbiologic and clinical studies, the following con-clusions can be made on using glass ionomer caries control:

1. Treating primary teeth with deeply cavitated carious lesions afterminimal excavation with glass ionomer caries control for 1–3months initially before instituting pulp therapy causes the bacte-ria to significantly decrease within the lesion (13, 14). In vital,symptomless teeth with apparent radiographic exposures or near

TABLE 1. All Types of Pulpotomy Usually Show Decreased Success over Time

References Pulpotomy Success(%)

Time(mo)

Dean et al. 2002 (18) Formocresol 92 6–12Huth et al. 2005 (19) 1/5 formocresol 85 24Rolling and Thylstrup

1975 (20)Formocresol 70 36

Vij et al. 2004 (11) Formocresol 70 40Smith et al. 2000 (21) Ferric sulfate 74–80 19Casas et al. 2004 (22) Ferric sulfate 67 36Eidelman et al. 2001 (23) MTA 100 13Jabbarifar et al. 2004 (24) MTA 94 12Holan et al. 2005 (25) MTA 91 38

NOTE. Internal root resorption was not always considered failure; Peng et al. (26) calculated MTA

success at 91%, counting internal resorption.

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exposures, treating them with caries control will likely stop cariesprogression (15).

2. GICC for 1–3 months changes the character of the dentin so thatit is drier and harder, and the affected dentin likely remineralizessimilar to dentin after stepwise excavation (7, 11, 14).

3. Using GICC as a diagnostic tool for 1–3 months in teeth withsymptomless radiographic exposures or ones with pain and ques-tionable vitality will diagnose those that can be treated success-fully with vital pulp therapy 98% of the time (16).

Is the Primary Tooth Pulpotomy out of Date forTreatment of Deep Caries and Should IPT Replace

Pulpotomy?Knowing the pulpal diagnosis of primary teeth with deep caries by

using GICC should greatly improve the chance of any vital pulp therapy.This leads to the article’s third purpose: Is IPT or pulpotomy the bestchoice for vital pulp therapy for deeply cavitated carious lesions?

Most pulpotomy success decreases over time from 90% or moreinitially (6 –12 months) to 70% or less after 3 years or more (11, 20,22) (Table 1, Figure 2). The MTA pulpotomy appears to have a higherlong-term success rate (�90%) than other pulpotomy types (23–25).Yet these reports generally are of shorter duration (only one �24months (25)) and have small sample sizes (�38 teeth) from which todraw strong conclusions. Most of these MTA pulpotomy studies wereperformed on teeth with symptomless radiographic exposures, andmost had immediate steel crowns placed after pulpotomy. The imme-diate crown should have minimized microleakage and increased pul-potomy success compared with a large amalgam (27), which had been

used in other pulpotomy studies (17, 27). A recent meta-analysis ofMTA versus formocresol pulpotomy studies suggested that MTA wassuperior to formocresol as a result of its lower failure rate (26).

IPT usually shows success rates of 90% or greater no matter thetechnique, medicament, or time periods (Table 2, Figure 2). IPT’slong-term success (3– 4 years) surpasses all other pulpotomy studies,with the possible exception of the 1 long-term MTA study (25). Therehave been various medicaments used for IPT, from calcium hydroxide(28 –30), glass ionomer (11, 17), to none (30), all of which did notsignificantly change IPT’s success rates, as shown in Table 2. Even usingdental students of vastly different abilities and likely different tech-niques, as reported by Al-Zayer et al. (29), did not significantly decreaseIPT’s success below 95%. The type of final, immediate restoration didnot alter IPT’s success when steel crowns were compared with compos-ite fillings and glass ionomers (11, 30). Even when no medicament wasplaced for IPT and the composite filling was bonded to the remainingdecay and decay-free dentin, Falster et al. (30) reported success greaterthan 90%.

How are pulpotomy and IPT being taught and practiced in theUnited States? Dunston and Coll (31) in 2005 surveyed 48 of the 56pediatric program directors in the U.S. dental schools and 689 of theboard-certified pediatric dentists. They found that 76% of the dentalschools taught either diluted or full-strength formocresol pulpotomy,whereas the other 24% taught ferric sulfate. Of the 689 pediatric den-tists, 81% used diluted or full-strength formocresol, 18% ferric sulfate,and 1% some other type of pulpotomy (electrocautery, MTA, etc). For-mocresol remains the overwhelming choice for pulpotomy, signifyingthe toxic concerns regarding formocresol do not seem to be a concernfor most schools or practicing dentists. The International Agency forResearch on Cancer stated in a 2004 press release that formaldehydecauses nasopharyngeal cancer (32). Milnes (33) in 2006 disputed thecancer concern by stating that the amount of formocresol in a pulpot-omy was likely such a small amount that formocresol pulpotomy was alow-exposure condition. Zazar et al. (34) found that when studying thewhite blood cells after formocresol pulpotomy in 20 children, 1 childshowed a 6-fold increase in white blood cell chromosomal abnormal-ities. From a statistical standpoint, they believed formocresol was notmutagenic, but further studies were needed to verify this.

The 2005 survey (31) also had a clinical scenario question re-garding deep caries removal in a primary second molar in a 5-year-old.Seventy percent of the program directors and more than 80% of thepediatric dentists reported that a pulpotomy was the treatment of choiceover IPT. It appears that IPT is not emphasized in U.S. dental schools asa method to treat deep asymptomatic caries, and most dentists practicethe way they were taught. In addition, most pediatric dentists believe it isbest to enter the pulp and do a formocresol pulpotomy, even thoughlong-term formocresol pulpotomy success is significantly lower thanIPT (11, 17, 20, 30).

Other factors need to be considered when choosing IPT or pulpo-tomy for deep caries in primary teeth. Vij et al. (11) studied IPT andpulpotomy success treating molars with reversible pulpitis pain. They

Figure 2. Long-term success rates of formocresol pulpotomy and IPT werestatistically different starting in the 2- to 3-year follow-up grouping. Reproducedwith permission from Forooq NS, Coll JA, Kuwabara A, Shelton P. Success ratesof formocresol pulpotomy and indirest pulp therapy in the treatment of deepdentinal caries in primary teeth. Pediatr Dent 2000;22:278 – 86.

TABLE 2. IPT Studies Show Success Rates of 90% or Greater over Time with Differing Techniques and Medicaments

IPT medicaments Success (%) Time (mo) Sample (N)

Nirschl and Avery 1983 (28) Calcium hydroxide 94 6 33Al-Zayer et al. 2003 (29) Calcium hydroxide 95 14 (median) 187Falster et al.* 2002 (30) — 90† 24 48Vij et al. 2004 (11) Glass ionomer 94 40 108Farooqet al. 2000 (17) Glass ionomer 93 50 55

*Adhesive resin alone without a liner or calcium hydroxide liner and adhesive resin.

†Combined success of both groups.

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reported that in 20 first primary molars with such pain, IPT success was85%, which was significantly better (P � .04) than the 53% in 19primary first molars treated with formocresol pulpotomy. They alsofound that there was significantly (P � .04) low success (61%) whenfirst primary molars were treated with formocresol pulpotomy com-pared with the 92% success with IPT in these molars. When the data ofHolan et al. (27) were tested with �2 analysis; it also showed a signifi-cantly lowered success for formocresol pulpotomy in primary first mo-lars.

Another concern in the choice of using IPT or pulpotomy is theearly exfoliation of pulpotomized teeth. More than 35% of formocresolpulpotomies exfoliate significantly earlier (�6 months) than nonpul-potomized teeth, whereas IPT-treated teeth exfoliate normally (11, 17).In addition, pulpotomies cost more than 2.3 times more than IPT, on thebasis of published dental insurance reimbursement for the 2 proce-dures (35, 36). In the United States, however, most dental insurers donot cover IPT for primary teeth, which might result in less utilization.For a tooth with deep caries 1 mm away from the pulp, IPT or pulpotomycan be performed. The pulpotomy could be more painful, becauseprofound anesthesia is always needed for a pulpotomy, whereas the IPTrequires no pulpal entry and, therefore, is potentially less painful.

When performing IPT and leaving residual decayed dentin, whatare the concerns of leaving this decay after a 1-visit IPT? Aponte et al.(37) reported performing indirect pulp capping with calcium hydrox-ide followed by amalgam restorations in 30 primary molars. After 6 – 46months (mean, 29 months), the amalgam and calcium hydroxide wereremoved, and the carious dentin that had been left behind cultured. In28 of 30 teeth (93%), the residual carious dentin was sterile. Oliveira etal. (15) studied 32 permanent teeth judged by radiographs to have apulp exposure. From digitized radiographs taken 6 –7 months afterpartial caries removal followed by temporary fillings, there was miner-alized improvement in the carious dentin over time. Finally, the 10-yearprospective study by Mertz-Fairhurst et al. (38) conclusively showedthat in 85 teeth after obvious occlusal caries was successfully sealedfrom microleakage, after 10 years in vivo, there was no progress of thecaries in permanent teeth.

The following conclusions on choosing IPT or pulpotomy can bedrawn from these studies:

1. Formocresol and ferric sulfate pulpotomy have a significantlylower long-term success for treatment of deep caries comparedwith IPT (11, 17, 20, 30). Most U.S. pediatric dentists currentlychoose to use formocresol pulpotomy over IPT (31).

2. IPT has been shown to have a significantly higher success rate forteeth with reversible pulpitis compared with formocresol pulpo-tomy (11).

3. IPT shows higher long-term success rates than any pulpotomyother than possibly MTA (Tables 1 and 2). MTA pulpotomy hasnot been shown to be effective in treating teeth with reversiblepulpitis.

4. IPT is less expensive, has fewer potential side effects, and does notexhibit early exfoliation as pulpotomy does (11, 17, 35, 36).

ConclusionsControversy persists as to the best way to perform vital pulp ther-

apy, and additional research is needed to see whether MTA pulpotomyperforms as well as IPT. From the present review of the literature andresearch, the following conclusions can be made:

1. Do not treat carious exposures in primary teeth with pulpotomyor direct pulp caps. Consider pulpectomy or extraction because

of the high chance of irreversible pulpitis and failure of vital pulptherapy after a carious pulp exposure.

2. For deep caries approaching the pulp, the choice of IPT or pul-potomy is up to the treating dentist.

3. Use glass ionomer caries control for deep cavitated lesions todiagnose the status of the pulp with or without history of pain toattain the highest success for vital pulp therapy. Stay out of thepulp by using IPT for a higher long-term chance of success com-pared with formocresol and ferric sulfate pulpotomy.

4. IPT has been shown to have a lower cost, higher success long-term, better exfoliation pattern, and better success treating re-versible pulpitis than pulpotomy.

References1. American Academy of Pediatric Dentistry. Clinical guidelines on pulp therapy for

primary and young permanent teeth: reference manual 2006-07. Pediatr Dent2006;28:144 – 8.

2. Rodd H. A pain in the pulp: innervation inflammation and management of the com-promised primary tooth pulp—synopses. Newsl Aust N Z Soc Paediatr Dent2005;32:3–5.

3. Reeves R, Stanley HR. The relationship of bacterial penetration and pulpal pathosis incarious teeth. Oral Surg 1966;22:59 – 65.

4. Shovelton DS. A study of deep carious dentin. Int Dent J 1968;18:392– 405.5. Lin L, Langeland K. Light and electron microscopic study of teeth with carious pulp

exposures. Oral Surg 1981;51:292–316.6. Bergenholtz G, Spangberg L. Controversies in endodontics. Crit Rev Oral Biol Med

2004;15:99 –114.7. Bjorndal L, Larsen T, Thylstrup A. A clinical and microbiological study of deep

carious lesions during stepwise excavation using long treatment intervals. Caries Res1997;31:411–7.

8. Leskell E, Ridell K, Cvek M, Majare I. Pulp exposure after stepwise vs direct completeexcavation of deep carious lesions in young posterior permanent teeth. Endod DentTraumatol 1996;12:192– 6.

9. Eidelman E, Ulmansky M, Michaeli Y. Histopathology of the pain in primary incisorswith deep dentinal caries. Pediatr Dent 1992;14:1372–5.

10. AAPD. Clinical guideline on pediatric restorative dentistry: reference manual 2006-07. Pediatr Dent 2006;28:136 – 43.


12. Bonecker M, Toi C, Cleaton-Jones P. Mutans streptococci and lactobaccili incarious dentin before and after atraumatic restorative treatment. J Dent 2003;31:423– 8.

13. Loyola-Rodriquez JP, Garcia-Godoy F, Lindquist R. Growth inhibition of glass iono-mer cements on mutans streptococci. Pediatr Dent 1994;16:346 –9.

14. Wambier DS, dos Santos FA, Guedes-Pinto AC, Jacqer RG, Simionato MRL. Ultra-structural and microbiological analysis of the dentin layers affected by carieslesions in primary molars treated by minimal intervention. Pediatr Dent2007;29:228 –34.

15. Oliveira EF, Carminatti G, Fontanella V, Maltz M. The monitoring of deep carieslesions after incomplete caries removal: results after 14-18 months. Clin Oral Investig2006;10:134 –9.

16. Campbell A, Coll JA. Thesis: diagnostic success of the glass ionomer sedative fillingdetermining pulpal vitality in primary molars with deep caries. Baltimore, MD:University of Maryland Pediatric Dental Department, 2007.

17. Forooq NS, Coll JA, Kuwabara A, Shelton P. Success rates of formocresol pulpotomyand indirest pulp therapy in the treatment of deep dentinal caries in primary teeth.Pediatr Dent 2000;22:278 – 86.

18. Dean JA, Mack RB, Fulkerson BT, Sanders BJ. Comparison of electrosurgical and formocresolpulpotomy procedures in children. Int J Paediatr Dent 2002;12:177–82.

19. Huth KC, Paschos E, Hajek-Al-Khatar N, et al. Effectiveness of 4 pulpotomy tech-niques: randomized controlled trial. J Dent Res 2005;84:1144 – 8.

20. Rolling I, Thylstrup A. A 3-year clinical follow-up study of pulpotomized primarymolars treated with formocresol technique. Scand J Dent Res 1975;83:47–53.

21. Smith NL, Seale NS, Nunn ME. Ferric sulfate pulpotomy in primary molars: a retro-spective study. Pediatr Dent 2000;22:192–9.

22. Casas MJ, Kenny DJ, Johnston DH, Judd PL. Long-term outcomes of primary molarferric sulfate pulpotomy and root canal therapy. Pediatr Dent 2004;26:44 – 8.

23. Eidelman E, Holan G, Fuks AB. Mineral trioxide aggregate vs formocresol in pulpo-tomized primary molars: a preliminary report. Pediatr Dent 2001;23:15– 8.

24. Jabbarifar SE, Khademi A, Ghasemi D. Success rate of formocresol pulpotomy vsmineral trioxide aggregate in human primary molar tooth. J Res Med Sci2004;6:304 –7.

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25. Holan G, Eidelman E, Fuks AB. Long-term evaluation of pulpotomy in primarymolars using mineral trioxide aggregate of formocresol. Pediatr Dent 2005;27:129 –36.

26. Peng L, Ye L, Tan H, Zhou X. Evaluation of the formocresol vs mineral trioxideaggregate primary molar pulpotomy: a meta-analysis. Oral Surg Oral Med Oral PatholOral Radiol Endod 2006;102:e40 – 4.

27. Holan G, Fuks AB, Keltz N. Success of formocresol pulpotomy in primary molarsrestored with steel crowns vs amalgam. Pediatr Dent 2002;24:212– 6.

28. Nirschl RF, Avery DR. Evaluation of a new pulp capping agent in indirect pulp therapy.J Dent Child 1983;50:25–30.


30. Falster CA, Araujo FB, Straffon LH, Nor JE. Indirect pulp treatment: In vivo outcomesof an adhesive resin system vs calcium hydroxide for protection of the dentin-pulpcomplex. Pediatr Dent 2002;24:241– 8.

31. Dunston B, Coll JA. A survey of primary tooth pulp therapy as taught in US dentalschools and practiced by diplomates of the American Board of Pediatric Dentistry.Pediatr Dent 2008;30:42– 48.

32. International Agency for Research on Cancer, World Health Organization. IARC clas-sifies formaldehyde as carcinogenic to humans. Press release no. 153, June 15, 2004.Available at: http://www.iarc.fr/ENG/Press_Releases/archives/pr153a.html.Accessed February 27, 2008.

33. Milnes AR. Persuasive evidence that formocresol use in pediatric dentistry is safe. JCan Dent Assoc 2006;72:247– 8.

34. Zazar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Jr LA. Formocresol muta-genicity following primary tooth pulp therapy: an in vivo study. J Dent2003;31:479 – 85.

35. Dental Benefits Plus fee schedule. Available at: http://www.dentalbenefitsplus.com/FeeSchedule/FeeScheduleDownload.asp. Accessed November 23, 2007.

36. Creighton International dental fee schedule for Pennsylvania. Available at: http://www.nationalinsurancestore.com/care/jump.htm. Accessed November 23, 2007.

37. Aponte AJ, Hartsook JT, Crowley MC. Indirect pulp capping verified. J Dent Child1966;33:164 – 6.

38. Mertz-Fairhurst EJ, Curtis JW, Ergle JW, Rueggeberg FA, Adair SM. Ultraconservativeand cariostatic sealed restorations: results at year 10. J Am Dent Assoc1998;129:55– 66.

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Is Formocresol Obsolete? A Fresh Look at the EvidenceConcerning Safety IssuesAlan R. Milnes, DDS, PhD

AbstractConcern has been expressed about the safety of for-mocresol use in pediatric dentistry. Formaldehyde, aprimary component in formocresol, is a hazardous sub-stance and is considered a probable human carcinogenby the International Agency for Research on Cancer,Health Canada, the Agency for Toxic Substances andDisease Registry in the U.S. Department of Health andHuman Services, and the U.S. Environmental ProtectionAgency. Humans inhale and ingest formaldehyde daily,however, and produce formaldehyde during cellular me-tabolism. The human body is physiologically equipped tohandle formaldehyde through multiple conversion path-ways. The resultant single carbon atom released duringmetabolism is deposited in the “1-carbon pool,” which, inturn, is used for the biosynthesis of macromoleculesincluding DNA and RNA. Reevaluation of earlier re-search that examined potential health risks associatedwith formaldehyde exposure has shown that this re-search was based on flawed assumptions, which re-sulted in erroneous conclusions. The purpose of thisreview was to examine more recent research aboutformaldehyde metabolism, pharmacokinetics, and car-cinogenicity. These results indicated that formaldehydeis probably not a potent human carcinogen under lowexposure conditions. Extrapolation of these researchresults to pediatric dentistry suggests an inconsequen-tial risk associated with formaldehyde use in pediatricpulp therapy. (J Endod 2008;34:S40-S46)

Key WordsCarcinogens, chemistry, formaldehyde, formocresol,pulpotomy, toxicity

The suggestion has been made recently that formocresol use in pediatric dentistry isunwarranted because of safety concerns, and consequently, formocresol use in

pediatric pulp therapy is obsolete. As a result, numerous investigations for alternativesto formocresol, some of which have shown efficacy equivalent to formocresol, havebeen completed. There can be no doubt that a reparative, biologic approach to pediatricpulp therapy is preferable to the absolutist, devitalization approach of formocresolpulpotomy or primary tooth pulpectomy, and research into alternatives is not onlywelcome but absolutely essential. This commentary will demonstrate, through a thor-ough review of the relevant literature, however, that the “evidence” for banning thismedicament because of safety concerns has been either misinterpreted or replaced bybetter science.

Ubiquity of FormaldehydeDaily formaldehyde exposure is a fact of life. Formaldehyde is found in the air we

breathe, the water we drink, and the food we eat (1). The World Health Organization(WHO) (2) has estimated that daily consumption of formaldehyde approximates1.5–14 mg/day (mean, 7.8 mg/day), although daily intake from food is difficult toevaluate. Owen et al (3) estimated that North Americans eating a typical North Americandiet ingest 11 mg/day. There are other numerous sources of formaldehyde exposure,which are summarized in Table 1. In unpopulated areas, outdoor air contains approx-imately 0.2 parts per billion (ppb) formaldehyde. In populated areas with truck andautomobile traffic, however, air concentrations range between 10 and 20 ppb. Therehave also been instances of high concentrations of formaldehyde in the air insidehomes. In 2002–2003, Health Canada (5) found formaldehyde levels of 2– 81 ppb inhomes in Prince Edward Island and Ottawa, Canada. Second-hand cigarette smokemight contain up to 0.4 ppm of formaldehyde (6). The National Institute for Occupa-tional Safety and Health (7) in the United States has stated that formaldehyde is imme-diately dangerous to health and life at concentrations of 20 parts per million (ppm) andhigher.

Assuming a contribution of 9.4 mg/day from food, 1 mg/day from inhalation, and0.15 mg/day from water, an adult takes in 10.55 mg of formaldehyde per day (1). Atpresent, there are no estimates of pediatric exposure, although it is likely that childrenare exposed to lower amounts because of lesser food intake.

The estimated formaldehyde dose associated with 1 pulpotomy procedure, assum-ing a 1:5 dilution of formocresol placed on a no. 4 cotton pellet that has been squeezeddry, is approximately 0.02– 0.10 mg.

Given the environmental ubiquity of formaldehyde and the recognized daily intakeby humans, it is highly unlikely that the elimination of the microgram quantities offormaldehyde associated with formocresol pulpotomy will have a significant impact ona child’s daily exposure.

Pharmacokinetics of FormaldehydeHumans produce endogenous formaldehyde as part of normal cellular metabo-

lism. Hileman (8) has shown that endogenous levels of metabolically produced form-aldehyde range from approximately 3–12 ng/g tissue. Amino acid metabolism, oxidativedemethylation, and purine and pyrimidine metabolism have all been shown to produceformaldehyde (9). Importantly however, human cells are physiologically equipped tomanage this exposure through multiple pathways for oxidation of formaldehyde toformate and incorporation into biologic macromolecules via tetrahydrofolate-depen-

Private practice in Kelowna, British Columbia, Canada.Address requests for reprints to Dr Milnes at

[email protected] of Interest: Alan R. Milnes, DDS, PhD, reports no

financial interests or potential conflicts of interest.0099-2399/$0 - see front matter



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S40 Milnes JOE — Volume 34, Number 7S, July 2008

dent, 1-carbon biosynthetic pathways. The single carbon atom releasedduring metabolism of formaldehyde and formate is deposited in the“1 carbon atom” pool, which, in turn, is used for the biosynthesis ofpurines, thymidine, and other amino acids that are incorporated intoRNA, DNA, and proteins during macromolecular synthesis.

Cytosolic alcohol dehydrogenase, mitochondrial aldehyde dehy-drogenase, and glutathione-dependent and glutathione-independentdehydrogenases are important enzymes in the metabolism of formalde-hyde in hepatocytes (10), oral mucosa (11), and nasal respiratorymucosa (12). Formate is the principal oxidative product of formalde-hyde, which is further oxidized to carbon dioxide and water by theaction of formyltetrahydrofolate synthetase (13). Formate might be con-verted to a soluble sodium salt via alternative pathways and excreted inthe urine, or it might be incorporated into the 1-carbon pool for use inbiosynthesis (14, 15).

Exogenous formaldehyde is taken up into the human body viaingestion, inhalation, and dermal exposure. Inhaled formaldehyde ap-pears to be readily absorbed by the upper respiratory tract, but it is notdistributed throughout the body because it is so rapidly metabolized(16). Ingested formaldehyde is readily absorbed by the gastrointestinaltract and exhibits little subacute toxicity after oral exposure (17). Ex-periments in humans, monkeys, and rats have shown no significantdifferences in formaldehyde concentration in the blood before and im-mediately after exposure by inhalation. Heck et al (16) used gas chro-matography and mass spectrometry to measure blood formaldehydeconcentrations in Fischer 344 rats exposed to a very high formaldehydeconcentration (14.4 ppm for 2 hours) and in unexposed controls.They showed that the blood concentrations of the 2 groups werevirtually identical. In rhesus monkeys, Casanova et al (18) reportedthat the formaldehyde concentrations in the blood after prolongedexposure to a high concentration of inhaled formaldehyde (6 ppmfor 6 hours per day, 5 days per week for 4 weeks) had no significanteffect on the formaldehyde concentration in blood relative to pre-exposure levels.

Human experiments have also provided compelling evidence thatinhaled formaldehyde has virtually no impact on blood concentrationsof formaldehyde. Heck et al (16) exposed 6 human volunteers for 40minutes to 1.9 ppm formaldehyde (a concentration that is considered

slightly irritating to the nasal and conjunctival membranes), but theconcentrations before exposure were not significantly different fromthose measured immediately after exposure. The average formaldehydeconcentration in the blood of rats, monkeys, and humans was 2.70 �0.15 �g/g (mean � standard error) or approximately 0.1 mmol/L. Indermal studies, formaldehyde was absorbed less readily by monkeysthan by rats or guinea pigs (19).

The half-life of formaldehyde molecules in monkey blood is about1.5 minutes after intravenous infusion (20). A concurrent rise in formicacid levels occurs, indicating formaldehyde’s metabolism (20). In rats,formaldehyde’s metabolism after administration via the pulp chamber isalso rapid, and the majority of conversion reportedly occurs within 2hours after administration (21). Exogenous formaldehyde has a bio-logic half-life of 1–1.5 minutes (22) and is quickly cleared from humanplasma. In dogs, the conversion of formate to carbon dioxide and waterresults in a biologic half-life for formate of about 80 –90 minutes (13).In humans, the liver converts formaldehyde to carbon dioxide at a rateof 22 mg/min (3, 23, 24).

In mice and rats, the metabolites of formaldehyde are elimi-nated in urine, feces, and expired air, with the relative proportiondepending on the route of administration (25, 26). Higher urineconcentrations of formic acid were found in 3 of 6 workers occu-pationally exposed to unspecified concentrations of formaldehydein air (30.0, 50.5, and 173.0 mg/L, respectively) than in unexposedworkers (17 mg/L) (27).

Formaldehyde also reacts covalently with amino and sulfhydrylgroups in target tissues and with DNA, forming unstable hydroxymethylprotein adducts (DNA-protein cross-links [DPX]) and, in a secondslower reaction involving recruitment of a second amino group, meth-ylene cross-links (28, 29). In rat and monkey tissues, however, metab-olism of formaldehyde and its elimination by pathways other than DPXformation overwhelmingly predominate (30).

Results from dental pulp studies involving rats, dogs, and monkeysshowed that formaldehyde labeled with radioactive carbon (14C) wasapparently distributed among the muscle, liver, kidney, heart, spleen,and lungs. The quantities of radiolabeled chemical detected, however,were very small (1% of the total administered dose) (21, 31–33). Myerset al (32) and Pashley et al (33) concluded that [14C]formaldehyde isabsorbed systemically from pulpotomy sites. These studies have beenwidely quoted as evidence that formaldehyde is distributed to distantsites. The investigators in these studies, however, did not determinewhether the labeling of tissues occurred by metabolic incorporation ofthe [14C] moiety of the labeled formaldehyde into macromolecules afterthe labeled formaldehyde molecule had been metabolized or by cova-lent binding (formation of protein adducts) by radiolabeled formalde-hyde molecules.

In an unrelated study, Casanova-Schmitz et al (34) sampled thevenous blood of rats after injecting either [14C]formaldehyde or[14C]formate into the tail vein. They verified that labeling of proteins andtarget tissues was due to metabolic incorporation of the radiolabeledmetabolite of formaldehyde, 14C, and not covalent binding. The profilesof radioactivity in the blood after these injections were similar, regard-less of whether [14C]formaldehyde or [14C]formate was the source of14C. These results excluded the possibility that the labeling of macro-molecules is due to formation of protein adducts by formaldehyde,because only [14C]formaldehyde is capable of forming protein adducts,whereas both [14C]formaldehyde and [14C]formate are precursors formacromolecular synthesis by the 1-carbon pool. Hence, it appears thatthe claims of systemic distribution in dental publications have beenoverstated and are, in fact, false.

TABLE 1. Sources of Human Formaldehyde Exposure (4)

Atmospheric formation: photochemical oxidation of organiccompounds

Internal combustion engine exhaustFertilizer productionHydrogen sulfide scavenger: oil operationsHousehold products:

Dishwashing liquidAntiseptics and disinfectantsCarpet cleanersCarpets

Preservatives and embalming solutionsCosmetics (maximum concentration, 0.3% v/v):

Fingernail hardeners (maximum concentration, 5% v/v)Paper productsAdhesivesTire and rubber manufacturingLatex paintsResin production:

Phenolic-formaldehyde resinUrea-formaldehyde resinPentaerythritol resin

Permanent press fabricsManufactured wood productsForest and brush firesTobacco products

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JOE — Volume 34, Number 7S, July 2008 Is Formocresol Obsolete? S41

Pharmacokinetics of CresolThe second active ingredient in formocresol, cresol, has received

little attention in the debate about formocresol safety or in investigationsof formocresol efficacy. Cresol has poor solubility, and because of this,it has been assumed that it does not enter systemic circulation (35).Cresol is highly lipophilic, however, and has been shown to completelydestroy cellular integrity, which presumably would allow for deepertissue fixation by the formaldehyde component of formocresol (35, 36).No data exist regarding cresol metabolism or elimination in humans orother mammals, and there is virtually no information about environ-mental sources of cresol to which humans might be exposed. Last, nohuman studies have been published that have examined plasma con-centration after exposure to cresol.

A recent clinical study in Colorado has reexamined the issue ofsystemic distribution of formocresol (37). Blood samples were drawnpreoperatively, intraoperatively, and postoperatively from 30 children,each of whom received comprehensive dental treatment including atleast 1 pulpotomy under general anesthesia. Blood samples were ex-amined for formaldehyde and cresol content by using gas chromatog-raphy and mass spectrometry detection. Neither formaldehyde norcresol was detected in any blood sample. Benzyl alcohol, however, aby-product of tricresol oxidation (38), was detected in microgramquantities in a dose-response fashion in blood samples collected afterplacement of formocresol-containing pellets.

Benzyl alcohol is present as a bacteriostatic preservative in manymultidose intravenous drugs and solutions (39). It also occurs naturallyin many plants, including raspberries and tea, and is an essential ingre-dient in many essential oils (39). Benzyl alcohol is oxidized rapidly tobenzoic acid, conjugated with glycine in the liver, and excreted as hip-puric acid. It has no carcinogenic or mutagenic potential, and the al-lowable daily intake, as established by WHO, is 5 mg/kg (39, 40).

Mutagenicity, Genotoxicity, and CytotoxicityExposure of cells to formaldehyde leads to the formation of DPX

(41). The most common types of DNA damage induced by formalde-hyde are clastogenic lesions, including sister chromatid exchanges(SCEs), micronuclei and chromosomal aberrations (42), and deletions(43). Levels of formaldehyde-induced DPX are considered to representa good molecular dosimeter of formaldehyde exposure at sites of con-tact and are frequently used for risk modeling and prediction of form-aldehyde carcinogenicity for different species (44 – 46). DPX have beenshown to occur only at the site of initial contact in the nasal mucosa ofrats and in the upper respiratory tract of monkeys exposed to formal-dehyde (45, 46).

It has also been proposed that formaldehyde could induce thedevelopment of DPX at distant sites, but no convincing evidence hasbeen obtained from in vivo experimental studies. The outcomes of thesestudies have included the following:

(1) lack of detectable protein adducts or DPX in the bone marrowof normal rats exposed to formaldehyde labeled with radioac-tive hydrogen (3H) or carbon (14C) at concentrations as highas 15 ppm (34);

(2) lack of detectable protein adducts or DPX in the bone marrowof glutathione-depleted (metabolically inhibited) rats exposedto [3H]formaldehyde and [14C]formaldehyde at concentra-tions as high as 10 ppm (22, 47);

(3) lack of detectable DPX in the bone marrow of rhesus monkeysexposed to [14C]formaldehyde at concentrations as high as 6ppm (46); and

(4) failure of formaldehyde to induce chromosomal aberrations inthe bone marrow of rats exposed to airborne concentrations as

high as 15 ppm (41) or of mice receiving intraperitoneal in-jections of formaldehyde at doses as high as 25 mg/kg (48).

Casas et al (49) have been critical of formocresol use in pediatricdentistry. They have regularly cited 2 studies as evidence of the geno-toxic and mutagenic effects of formaldehyde (50, 51). Those publishedarticles, in fact, represent the same study, however, with the first articlereporting interim results of nasal tumor development in rodents (50)and the second (3 years later) (51) reporting the final results for thesame study. Although Kerns et al (51) discussed the formaldehyde’smutagenic potential in their animal model, they did not report resultspertaining to mutagenicity, as was stated by Casas et al.

More recent research by Heck and Casanova (52) has revealedthat the development of DPX in the nasal tissues of rats and the upperrespiratory tracts of primates is associated only with exposure to highdoses of formaldehyde. At ambient concentrations consistent with en-vironmental exposures, DPX are unlikely to occur. Furthermore,Quievryn and Zhitkovitch (53) have shown that DPX do not persist intissues for more than a few hours and undergo either spontaneoushydrolysis or active repair by proteolytic degradation of cross-linkedproteins. This calls into question the role of DPX in formaldehyde-induced carcinogenesis.

Cytogenetic studies (54) of lymphocytes from rodents after form-aldehyde inhalation with exposures ranging from 0.5–15 ppm for 6hours per day for 5 days failed to detect either chromosomal aberra-tions or SCEs at any of the formaldehyde concentrations. The authorsattributed their negative results to formaldehyde’s pharmacokinetics.

In vitro experiments with a Chinese hamster cell line (43) foundthat DPX and SCE, as a result of formaldehyde exposure, were associatedwith cytotoxicity, not mutation (55). In addition, no mutagenesis oc-curred in cultured human lymphocytes below a formaldehyde thresholdof 5 �g/mL in the culture medium (56).

Dental studies have not supported the contention that formalde-hyde, as used in dentistry, is mutagenic. Zarzar et al (57) performedformocresol pulpotomy on 20 children by using Buckley’s original for-mula (19% formaldehyde and 35% cresol in a solution of 15% glycerinand water). Peripheral venous samples were collected from each childimmediately before and 24 hours after the pulpotomy, and lymphocyteswere collected from each blood sample for cell culture and cytogeneticanalysis. No statistically significant differences were found between the2 groups in terms of chromosomal aberrations, chromatid breaks, orchromatid gaps. Also, Zarzar et al concluded that formocresol is notmutagenic. The authors observed chromosomal aberrations in 1 (5%)of the 20 patients but were unable to determine whether formocresol orother variables accounted for this finding.

Ribeiro et al (58, 59) reported 2 studies that assessed the muta-genic potential of formocresol as well as several other chemicals com-monly used in dentistry. With a mouse lymphoma cell line, culturedhuman fibroblasts, and a series of formocresol dilutions similar toclinical doses, these authors found that formocresol did not producedetectable DNA damage and should not be considered genotoxic.

Laboratory investigations of root canal sealers containing formal-dehyde, which are used in endodontic procedures, have demonstratedcytotoxicity (60). For several reasons, however, these investigations arenot comparable to formocresol pulp studies. A larger quantity of form-aldehyde is released from root canal sealers than during pediatric for-mocresol pulpotomy because of the large quantity of sealer used. More-over, contact of formocresol with vital pulp tissue during pulpotomy isrestricted to only a few minutes, whereas root canal sealer remains inthe root canal and forms part of the final restoration, with the potentialfor further release of formaldehyde.

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In summary, DPX’s development has been demonstrated only afterprolonged exposure to formaldehyde at specific contact sites such as thenasopharynx. Hence, the argument that the microgram quantities offormaldehyde applied to pediatric pulp tissue for a few minutes willinduce distant-site genotoxicity is not supported by the available evi-dence.

CarcinogenicityIt is indisputable that cancer develops in experimental animals

after inhalation of air with high concentrations of formaldehyde. Thesecancers occur as a result of long-term, direct contact between the form-aldehyde and susceptible tissues. The resultant toxic effects at theseinitial contact sites include ulceration, hyperplasia, and squamousmetaplasia and “are considered to contribute to the subsequent devel-opment of cancer” (61). These high-dose responses, however, are un-likely to occur at sites distant from the point of initial formaldehydecontact (such as the bone marrow). This is because, according to alarge body of undisputed evidence, formaldehyde is not delivered tothese distant sites. Those who have argued against the continued use offormocresol in pediatric dentistry on the basis that “formaldehydecauses cancer” have failed to recognize this very important distinction.

Those opposed to formocresol use in pediatric dentistry have citedthe work of Swenberg et al (50) and Kerns et al (51) to support theirargument about carcinogenicity. These 2 studies are, in fact, the samestudy, with Swenberg et al reporting interim results after 18 months andKerns et al reporting final results for the same study after 30 months.This group of researchers showed that nasal squamous cell carcinomadeveloped in Fischer 344 rats exposed to formaldehyde gas at concen-trations of 6 ppm and higher for 6 hours per day, 5 days per week for 24months. The formaldehyde concentrations that resulted in cancer, how-ever, were more than 1000 times the typical human environmentalexposure and 8 times the U.S. occupational exposure limit (0.75 ppm)(62). Therefore, they are not representative of human experience.Moreover, the experimental conditions that resulted in nasal cancers inrodents in no way resemble the conditions associated with a 5-minuteexposure to microgram quantities of formaldehyde, as experienced by achild undergoing formocresol pulpotomy.

Until recently, formaldehyde was classified as a “probable humancarcinogen” by Health Canada (63, 64), the International Agency forResearch on Cancer (IARC) (65, 66), the Agency for Toxic Substancesand Disease Registry (ATSDR) (62, 67) in the U.S. Department of Healthand Human Services, and the U.S. Environmental Protection Agency(USEPA) (68). Although they lacked sufficient evidence to demonstratethe development of cancer in exposed humans, these regulators (HealthCanada, ATSDR, and USEPA) and advisory agency (IARC) predicted thecancer risk posed by low-dose exposure by extrapolating from the lab-oratory animal data previously cited.

Various researchers, however, have recognized that significantanatomic and physiologic differences between humans and other ani-mal models have confounded extrapolation of animal data to humans(29, 69 –71). Researchers at the Chemical Industry Institute for Toxi-cology Centers for Health Research (CIIT) (70, 71) developed dynamic3-dimensional airflow models that accurately depicted both airflow andregional deposition of formaldehyde on mucosal surfaces of rodents,monkeys, and humans. The improved understanding garnered from thisresearch allowed the researchers to improve the accuracy of computer-generated predictions of the uptake and absorption of formaldehyde ineach animal model. The CIIT researchers also developed a biologicallymotivated computational model, on the basis of combined rodent andprimate data from the computer-generated nasal cavity airflow models,cell proliferation data, and DPX data. This model allowed them to math-

ematically evaluate the cancer risks associated with formaldehyde in-halation (71).

Finally, with input from the USEPA, Health Canada, and peer re-viewers, the CIIT researchers published a thorough evaluation of po-tential cancer risk from formaldehyde, integrating toxicologic, mecha-nistic, and dosimetric data (55). These new experimental data, derivedfrom sophisticated mathematical models, replaced the inaccurate de-fault assumptions that had been used by the regulatory authorities.

On the basis of these investigations (55, 71), CIIT suggested thatcancer risk is negligible until formaldehyde exposure reaches the levelsassociated with cytotoxicity (in the range of 600 –1000 ppb). The re-sulting estimates of cancer risk are many orders of magnitude lowerthan the 1987 and 1991 USEPA estimates (55, 71). The model devel-oped by CIIT overcomes problems associated with the standard riskassessment methods cited by the USEPA and the IARC.

A 2004 IARC press release (66) reclassified formaldehyde from a“probable” to a “known” human carcinogen and has been cited asevidence that formaldehyde should be eliminated from pediatric den-tistry (49). Some clarification of the press release is required, however,or readers will be left with the impression that the IARC classification isdefinitive and binding. The IARC classification is not an assessment ofrisk but merely an attempt to answer the question of whether, under anycircumstances, a substance could produce cancer in humans. Clearly,for formaldehyde the answer to this question is yes. In fact, the authorrequested clarification from the head of the IARC Monographs Pro-gramme regarding a threshold dosage for carcinogenicity of formalde-hyde. Dr Vincent Cogliano responded “the evaluations at IARC Mono-graph meetings concern only whether an agent can increase the risk ofcancer at some dose. We do not undertake dose-response analyses,consequently, we did not discuss a possible threshold” (personal com-munication, August 5, 2005).

Thus, the IARC classification serves as a hazard identification, thefirst step in a multilevel risk assessment process. More importantly, theIARC reclassification was based primarily on the results of a singleNational Cancer Institute (NCI) study (44) among workers in formal-dehyde industries. That study included many workers at several plants,but only a small number of people working at a single plant were foundto have a rare form of cancer. Clearly, confounding variables might haveaffected the results. Recognizing these uncertainties, the NCI has agreedto update the study.

Health Canada has stated that it considers the CIIT dose-responsemodel (71) “to provide the most defensible estimates of cancer risk, onthe basis that it encompasses more of the available biological data,thereby offering considerable improvement over default” (72). TheOrganization for Economic Cooperation and Development has stated,on the basis of the CIIT research models, that “taking into account theextensive information on its mode of action, formaldehyde is not likelyto be a potent carcinogen to humans under low exposure conditions”(73). Pediatric pulp therapy with formocresol as recommended wouldbe considered a “low exposure condition.” The USEPA Office of AirQuality Planning and Standards has stated, “The dose response value inthe EPA Integrated Risk Information System (for formaldehyde) isbased on a 1987 study and no longer represents the best availablescience in the peer-reviewed literature. We believe that the CIIT mod-eling effort represents the best available application of mechanistic anddosimetric science on the dose-response for portal of entry cancers dueto formaldehyde exposure” (74).

The possibility that inhaled or ingested formaldehyde might inducecancers at sites distant from the respiratory or gastrointestinal tracts hasbeen investigated in numerous long-term toxicity studies performed inrodents (61). Leukemia was not observed in any of 7 long-term inha-lation bioassays in rodents, and it was not observed in 3 drinking water

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studies in which rodents were exposed to doses as high as 1.9 –5 g/L.Leukemia was observed in a single drinking water study (75), in whichWistar rats were exposed to doses as high as 1.5 g/L. That study, how-ever, is regarded by the Cancer Assessment Committee of the U.S. Foodand Drug Administration (76) as questionable, and the data are unre-liable because of a lack of critical detail and questionable histopatho-logic conclusions.

Evidence from epidemiology investigations of industrial workerswith exposure to formaldehyde provides weak and inconsistent evi-dence that such exposure is associated with leukemia. Importantly, theresearchers in each instance failed to use recognized epidemiologiccriteria to evaluate the hypothesis that formaldehyde exposure leads tocancer. The results of 2 large American studies, one from the NCI (44)and the other from the National Institute of Occupational Safety andHealth (77), did not support a strong causal relation between formal-dehyde exposure and leukemia. The strength of association—the extentto which a collective body of data indicates a positive association be-tween a disease, in this case leukemia, and a suspected causative agent,in this case formaldehyde — was weak (standardized mortality ratio,0.86). Moreover, a study of British chemical workers, sponsored by theMedical Research Council Environmental Epidemiology Unit in theUnited Kingdom (78) and involving the highest chronic formaldehydeexposures and highest peak exposures of all 3 investigations, showed nocausal relationship between formaldehyde and leukemia.

Therefore, evidence from both experimental investigations andepidemiologic research does not support the hypothesis that inhaled oringested formaldehyde might induce distant-site toxicity. The abundantnegative evidence mentioned previously is undisputed and strongly sug-gests that there is no delivery of inhaled, ingested, or topically appliedformaldehyde to distant sites. The facts are that formaldehyde occursnaturally throughout the body, there are multiple pathways for detoxi-fication, and only microgram quantities of formaldehyde are applied topulp tissues during pulpotomy procedures for mere minutes. Consid-ering these facts, the negative findings provide convincing evidence thatexposure of children to the formaldehyde component of formocresolduring a pulpotomy is insignificant and inconsequential.

Immune SensitizationDespite evidence from dogs that formocresol can produce anti-

genic activity in dental pulp tissue (79), Rolling and Thulin (80) foundno increase in either immune response or allergic reactions in 128children who had undergone formocresol pulpotomy.

More recent evidence supports the work of Rolling and Thulin(80). A Canadian study (81) of urea formaldehyde foam insulation fromproducts in the homes of asthmatic subjects found that long-term ex-posure had no effect on immunologic parameters. Doi et al (82) foundthat the prevalence of immunoglobulin E sensitization to formaldehydewas very low among Japanese children, regardless of whether they hadasthma; furthermore, they found no clinical relevance of formaldehyde-specific immunoglobulin E. Hence, the suggestion that formocresol“sensitizes” children has not been supported.

Where Do We Go From Here?On the basis of the evidence presented in this review, it is highly

unlikely that formocresol, judiciously used, is genotoxic or immuno-toxic or poses a cancer risk to children who undergo one or moreformocresol pulpotomy procedures. Definitive data to support this hy-pothesis are lacking, however, and such evidence is needed beforedefinitive conclusions can be reached.

In keeping with accepted therapeutic principles, pediatric dentistswho wish to continue to use formocresol should apply the lowest dose

possible for the shortest time possible to obtain the desired effect. Tothat end, a 1:5 dilution of Buckley’s formocresol is recommended. Thedilution should be performed in the local pharmacy to ensure accuracy.Recent research (83) has indicated that a minority of pediatric dentistsuse diluted formocresol because it is not available commercially, soperhaps it is time for the formocresol product manufacturers to developand market a 1:5 dilution of this medicament to replace the “full-strength” formulations now available, especially given that the effects ofthe 2 formulations are equivalent (83).

No data exist to verify the actual amount of formocresol deliveredto the pulp during the performance of a formocresol pulpotomy. Resultsfrom a yet to be published study in Colorado of systemic formocresoldistribution in children receiving at least 1 pulpotomy while undergeneral anesthesia determined that the mean dose of formocresolwithin a cotton pellet was 0.013 mg (37). This study used full-strengthformocresol. Presumably, if a 1:5 dilution had been used, the meanmilligram dose per pellet would have been 0.0026 mg. The actual dosethat interacts with the pulp tissue is probably much smaller in bothcases, however, because most of the formocresol will remain in thecotton pellet. Determining the actual doses delivered to the pulp repre-sents an important area for further investigation. In addition, efforts areneeded to disseminate information about dose delivered to both theprofession and the public.

Evidence continues to accumulate that supports the successfulapplication of indirect pulp treatment (IPT) procedures to primaryteeth as well as the use of mineral trioxide aggregate (MTA) in pulpot-omy procedures. A Cochrane systematic review by Nadin et al (84) in2003 suggested that the paucity of randomized controlled trials in pe-diatric pulp therapy made it virtually impossible to make recommenda-tions regarding pulpotomy procedures. Nevertheless, numerous ran-domized controlled trials examining both IPT and MTA have since beenpublished. These investigations have shown that both IPT and MTA haveclinical and radiographic results that are equivalent to or better thanthose produced by formocresol over time. The reader is referred toarticles in this issue by Fuks and Coll for more detail about these prom-ising alternatives.

It is important to put this discussion into a broader perspective.Antibiotics are used in dentistry at least as often as formocresol, andeach year numerous children and adults are injured or die as a result ofallergic or anaphylactic reactions to antibiotics (85), yet there has beenno call for the elimination of antibiotics from dental practice. In fact,there is an acceptance that an allergic reaction is both a possibility anda risk in the treatment of dental infection. Peroxides for dental bleach-ing, bonding agents, and solvents used in adhesive dentistry all demon-strate cytotoxicity in vitro (86), yet they form an important part of everydentist’s restorative armamentarium. These chemicals are used in pe-diatric dentistry without warnings to parents and patients of the associ-ated risks. Diagnostic radiation is an indispensable component of everydental office, yet irrefutable evidence (87) exists showing that radiationexposure can induce the development of cancers. Singling out onechemical such as formocresol for elimination from practice protocolsin the face of a complete lack of human experimental data identifying aclear risk is intellectual tomfoolery.

On the basis of the evidence presented in this review, the risk ofcancer, mutagenesis, or immune sensitization associated with theproper use of formocresol in pediatric pulp therapy can be consideredinconsequential. Until a superior alternative is developed or there isdefinitive evidence substantiating a cancer risk, there is no reason todiscontinue its use. When used judiciously, formocresol is a safe medi-cament.

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ConclusionsEvidence presented in this review of the literature indicates that

formocresol, when used judiciously, is unlikely to be genotoxic, immu-notoxic, or carcinogenic in children when used in pulpotomy proce-dures. Until a biologic and reparative alternative has been identified thatis clearly and reproducibly superior to formocresol, there are no sci-entific or toxicologic reasons to abandon formocresol in pediatric den-tistry.

References1. Federal-Provincial-Territorial Committee on Drinking Water. Formaldehyde: guide-

lines for Canadian drinking water quality—supporting documents. Available at:www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/doc_sup-appui/index_e.html. AccessedMarch 13, 2006.

2. World Health Organization. Formaldehyde: environmental health criteria 89, Inter-national Programme on Chemical Safety, Geneva, 1989. Available at: www.who.int/ipcs/publications/ehc/ehc_numerical/en/. Accessed March 13, 2006.

3. Owen BA, Dudney CS, Tan EL, Easterly CE. Formaldehyde in drinking water: com-parative hazard evaluation and an approach to regulation. Regul Toxicol Pharmacol1990;11:220 –36.

4. Canadian Environmental Protection Act, 1999. Priority substances list assessmentreport: formaldehyde. Environment Canada, Health Canada. Available at: www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl2-lsp2/formaldehyde/index_e.html. Ac-cessed July 22, 2007.

5. Health Canada. It’s your health: formaldehyde and indoor air. Available at: www.hc-sc.gc.ca/iyh-vsv/environ/formaldehyde_e.html. Accessed March 13, 2006.

6. Manitoba Federation of Labour Occupational Health Centre, Inc. Formaldehyde.Available at: www.mflohc.mb.ca/fact_sheets_folder/formaldehyde.html. AccessedMarch 13, 2006.

7. The National Institute for Occupational Safety and Health. Formaldehyde. Availableat: www.tricornet.com/nioshdbs/idlh/50000.htm. Accessed March 13, 2006.

8. Hileman B. Formaldehyde: assessing the risk. Environ Sci Technol 1984;18:216a–21a.

9. Squire RA, Cameron LL. An analysis of potential carcinogenic risk from formalde-hyde. Regul Toxicol Pharmacol 1984;4:107–29.

10. Teng S, Beard K, Pourahmad J, et al. The formaldehyde metabolic detoxificationenzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes.Chem Biol Interact 2001;130:285–96.

11. Hedberg JJ, Hoog JO, Nilsson JA, Xi Z, Elfwing A, Grafstrom RC. Expression of alcoholdehydrogenase 3 in tissue and cultured cells from human oral mucosa. Am J Pathol2000;157:1745–55.

12. Dahl A. Possible consequences of cytochrome P-450-dependent monoxygenases innasal tissues. In: Barrow C, ed. Toxicology of the nasal passages. Washington, DC:Hemisphere Publishing, 1986:263–73.

13. Malorny G, Rietbrock N, Schneider M. [Oxidation of formaldehyde to formic acid inblood, a contribution to formaldehyde metabolism.] Naunyn Schmiedenbergs ArchExp Pathol Pharmakol 1965;250:419 –36.

14. Bardana EJ, Montanaro A. Formaldehyde: an analysis of its respiratory, cutaneous,and immunologic effects. Ann Allergy 1991;66:441–58.

15. Kitchens JF, Castner RE, Edwards GS, Harward III WE, Macri BJ. Investigation ofselected potential environmental contaminants: formaldehyde. Washington, DC: USEnvironmental Protection Agency, 1976: EPA-560/2-76-009.

16. Heck HD, Casanova-Schmitz M, Dodd PB, Schachter EN, Witek TJ, Tosun T. Formal-dehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposedto CH2O under controlled conditions. Am Ind Hyg Assoc J 1985;46:1–3.

17. Johannsen FR, Levinskas GJ, Tegeris AS. Effects of formaldehyde in the rat and dogfollowing oral exposure. Toxicol Lett 1986;30:1– 6.

18. Casanova M, Heck H, Everitt JI, Harrington WW Jr, Popp JA. Formaldehyde concen-trations in the blood of rhesus monkeys after inhalation exposure. Food Chem Toxi-col 1988;26:715– 6.

19. Jeffcoat AR, Chasalow F, Feldman DB, Marr H. Disposition of [14C] formaldehydeafter topical exposure to rats, guinea pigs and monkeys. In: Gibson JE, ed. Formal-dehyde toxicity. Washington, DC: Hemisphere Publishing, 1983:38 –50.

20. McMartin KE, Martin-Amat G, Noker PE, Tephly TR. Lack of a role for formaldehydein methanol poisoning in the monkey. Biochem Pharmacol 1979;28:645–9.

21. Ranly DM. Assessment of the systemic distribution and toxicity of formaldehydefollowing pulpotomy treatment: part one. J Dent Child 1985;52:4331– 4.

22. Bhatt HS, Lober SB, Combes B. Effect of glutathione depletion on aminopyrine andformaldehyde metabolism. Biochem Pharmacol 1988;37:1581–9.

23. Waydhas C, Weigl K, Seis H. The disposition of formaldehyde and formate arising fromdrug N-demethylations dependent on cytochrome P-450 in hepatocytes and perfusedrat liver. Eur J Biochem 1978;89:143–50.

24. McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning: V—role offormate metabolism in the monkey. J Pharmacol Exp Ther 1977;201:564 –72.

25. Galli CL, Ragusa C, Resmini P, Marinovich M. Toxicological evaluation in rats andmice of the ingestion of a cheese made from milk with added formaldehyde. FoodChem Toxicol 1983;21:313–7.

26. Upreti RK, Farooqui MY, Ahmed AE, Ansari GA. Toxicokinetics and molecular inter-action of [14C]-formaldehyde in rats. Arch Environ Contam Toxicol 1987;16:263–73.

27. Srivastava AK, Gupta BN, Gaur JS, Bihari V. Clinical evaluation of workers handlingmelamine formaldehyde resin. Clin Toxicol 1992;30:677– 81.

28. Bolt HM. Experimental toxicity of formaldehyde. J Cancer Res Clin Oncol1987;113:305–9.

29. Nilsson JA, Zheng X, Sundqvist K, et al. Toxicity of formaldehyde to human oralfibroblasts and epithelial cells: influences of culture conditions and role of thiolstatus. J Dent Res 1998;77:1896 –903.

30. Heck H, Casanova M. The implausibility of leukemia induction by formaldehyde: Acritical review of the biological evidence on distant-site toxicity. Regul Toxicol Phar-macol 2004;40:92–106.

31. Myers DR, Pashley DH, Whitford GM, McKinney RV. Tissue changes induced by theabsorption of formocresol from pulpotomy sites in dogs. Pediatr Dent 1983;5:6 – 8.

32. Myers D, Shoaf K, Dirksen T, Pashley DH, Whitford GM, Reynolds KE. Distribution of14C-formaldehyde after pulpotomy with formocresol. J Am Dent Assoc 1978;96:805–13.

33. Pashley E, Myers D, Pashley DH, Whitford G. Systemic distribution of14C-formaldehyde from formocresol-treated pulpotomy sites. J Dent Res 1980;59:602– 8.

34. Casanova-Schmitz M, Starr TB, Heck HD. Differentiation between metabolic incor-poration and covalent binding in the labeling of macromolecules in the rat nasalmucosa and bone marrow for inhaled 14C- and 3H-formaldehyde. Toxicol Appl Phar-macol 1984;76:26 – 44.

35. Ranly D. Formocresol toxicity: current knowledge. Acta Odontol Pediatr 1984;5:93– 8.

36. Loos P, Hans SS. An enzyme histochemical study of the effect of various concentra-tions of formocresol on connective tissues. Oral Surg Oral Med Oral Pathol1971;31:571– 85.

37. Kahl J, Personal communication, August 2006; http://www.thechildrenshospital.org/news/publications/practiceupdate/2007/formocresol.aspx. Accessed November 12,2007.

38. Gruber C. The pharmacology of benzyl alcohol and its esters. J Lab Clin Med1923;9:15.

39. International Programme on Chemical Safety. Environmental health criteria 89:formaldehyde. Available at: http://www.inchem.org/documents/ehc/ehc/ehc89.htm.Accessed March 13, 2007.

40. U.S. Environmental Protection Agency. Integrated risk information system: tricresol(CASRN 1319-77-77-3). Available at: http://www.epa.gov/iris/subst/0030.htm. Ac-cessed November 12, 2007.

41. Heck HD, Casanova M, Starr TB. Formaldehyde toxicity: new understanding. Crit RevToxicol 1990;20:397– 426.

42. Merk O, Speit G. Significance of formaldehyde-induced DNA-protein crosslinks formutagenesis. Environ Mol Mutagen 1998;32:260 – 8.

43. Crosby RM, Richardson KK, Craft TR, Benforad KB, Liber HL, Skopek TR. Molecularanalysis of formaldehyde-induced mutations in human lymphoblasts and E. coli.Environ Mol Mutagen 1988;12:155– 66.

44. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from hematopoieticmalignancies among workers in formaldehyde industries. J Natl Cancer Inst2003;95:1615–23.

45. Casanova M, Deyo DF, Heck HD. Covalent binding of inhaled formaldehyde to DNA inthe nasal mucosa of Fischer 344 rats: analysis of formaldehyde and DNA by high-performance liquid chromatography and provisional pharmacokinetic interpreta-tion. Fundam Appl Toxicol 1989;12:397– 417.

46. Casanova M, Morgan KT, Steinhagen WH, Everitt JI, Popp JA, Heck HD. Covalentbinding of inhaled formaldehyde to DNA in the respiratory tract of rhesus monkeys:pharmacokinetics, rat-to-monkey interspecies scaling, and extrapolation to man.Fundam Appl Toxicol 1991;17:409 –28.

47. Casanova M, Heck H. Further studies of the metabolic incorporation and covalentbinding of inhaled [3H]- and [14C]-formaldehyde in Fischer-344 rats: effects ofglutathione depletion. Toxicol Appl Pharmacol 1987;89:105–21.

48. Natarajan AT, Darroudi F, Bussman CJM, van Kesteren-van Leeuwen AC. Evaluation ofthe mutagenicity of formaldehyde cytogenetic assays in vivo and vitro. Mutat Res1983;122:355– 60.

49. Casas MJ, Kenny DJ, Judd PL, Johnston DH. Do we still need formocresol in pediatricdentistry? J Can Dent Assoc 2005;71:749 –51.

50. Swenberg JA, Kerns WD, Mitchell RI, Gralla EJ, Pavkov KL. Induction of squamous cellcarcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor.Cancer Res 1980;40:3398 – 402.

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51. Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, Swenberg JA. Carcinogenicity of form-aldehyde in rats and mice after long-term inhalation exposure. Cancer Res1983;43:4382–92.

52. Heck H, Casanova M. Pharmacodynamics of formaldehyde: application of a model forthe arrest of DNA replication by DNA-protein cross-links. Toxicol Appl Pharmacol1999;160:86 –100.

53. Quievryn G, Zhitkovich A. Loss of DNA-protein crosslinks from formaldehyde ex-posed cells occurs through spontaneous hydrolysis and an active repair processlinked to proteosome function. Carcinogenesis 2000;21:1573– 80.

54. Kligerman AD, Phelps MC, Erexson GL. Cytogenetic analysis of lymphocytes from ratsfollowing formaldehyde inhalation. Toxicol Lett 1984;21:241– 6.

55. Chemical Industry Institute for Technology. Formaldehyde: hazard characterizationand dose-response assessment for carcinogenicity by the route of inhalation: positionpaper. Research Triangle Park, NC: CIIT; 1999.

56. Kreiger RA, Garry VF. Formaldehyde-induced cytotoxicity and sister-chromatid ex-changes in human lymphocyte cultures. Mutat Res 1983;120:51–5.

57. Zarzar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Junior LA. Formocresolmutagenicity following primary tooth pulp therapy: An in vivo study. J Dent2003;31:479 – 85.

58. Ribeiro DA, Marques ME, Salvadori DM. Lack of genotoxicity of formocresol, par-amonochlorophenol, and calcium hydroxide on mammalian cells by comet assay. JEndod 2004;30:593– 6.

59. Ribeiro DA, Scolastici C, De Lima PL, Marques ME, Salvadori DM. Genotoxicity ofantimicrobial endodontic compounds by single cell gel (comet) assay in Chinesehamster ovary (CHO) cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod2005;99:637– 40.

60. Huang TH, Ding SJ, Hsu TZ, Lee ZD, Kao CT. Root canal sealers induce cytotoxicity andnecrosis. J Material Sci Mater Med 2004;15:767–71.

61. International Agency for Research on Cancer. Formaldehyde. IARC Monogr EvalCarcinog Risks Hum 1996;62:217–375.

62. US Department of Labor, Occupational Safety & Health Administration. Safety andhealth topics: formaldehyde. Available at: www.osha.gov/SLTC/formaldehyde. Ac-cessed March 13, 2006.

63. Canadian Environmental Protection Act. Priority substances list assessment report:formaldehyde. Available at: www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/contaminants/psl2-lsp2/formaldehyde/formaldehyde_e.pdf. Accessed March13, 2007.

64. Health and Welfare Canada. Exposure guidelines for residential indoor air quality.Ottawa, Ontario, Canada: Department of National Health and Welfare, 1987.

65. International Agency for Research on Cancer. World Health Organization, Suppl 7.Overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to42, 1987.

66. IARC, WHO. IARC classifies formaldehyde as carcinogenic to humans: press releaseno. 153. Available at: www.iarc.fr/ENG/Press_Releases/archives/pr153a.html. Ac-cessed March 13, 2006.

67. Agency for Toxic Substances and Disease Registry. Toxicological profile for formal-dehyde: US Department of Health and Human Services, Public Health Service. Avail-able at: www.atsdr.cdc.gov/toxprofiles/tp111.html. Accessed March 13, 2006.

68. US Environmental Protection Agency. Integrated risk information system. IRIS data-base for risk assessment. Washington, DC. Available at: www.epa.gov/iris. AccessedMarch 13, 2006.

69. Schlosser PM, Lilly PD, Conolly RB, Janszen DB, Kimbell JS. Benchmark dose riskassessment for formaldehyde using airflow modeling in a single-compartment: DNA-protein cross-link dosimetry model to estimate human equivalent doses. Risk Anal2003;23:473– 87.

70. Kimbell JS, Subramaniam RP, Gross EA, Schlosser PM, Morgan KT. Dosimetry mod-eling of inhaled formaldehyde: comparisons of local flux predictions in the rat,monkey, and human nasal passages. Toxicol Sci 2001;64:100 –10.

71. Conolly RB, Kimbell JS, Janszen D, et al. Human respiratory tract cancer risks ofinhaled formaldehyde: dose response predictions derived from biologically moti-vated computational modeling of a combined rodent and human dataset. Toxicol Sci2004;82:279 –96.

72. Environment Canada and Health Canada. Existing substances evaluation: assessmentreport—formaldehyde. Available at: www.ec.gc.ca/substances/ese/eng/psap/final/formaldehyde.cfm. Accessed March 13, 2006.

73. Organization for Economic Development and Cooperation. Screening informationdata set, initial assessment profile. Available at: www.oecd.org/dataoecd/24/22/31744923.pdf. Accessed March 13, 2007.

74. U.S. Evironmental Protection Agency Office of Air Quality Planning and Standards,EPA Office of Air and Radiation. Rule issued under maximum achievable controltechnology provisions of the Federal Clean Air Act. 69 Federal regulation 18333, April7, 2004. Fed Regist 2004;69:18333– 4.

75. Soffritti M, Maltoni C, Maffei F, Biagi R. Formaldehyde: an experimental multipoten-tial carcinogen. Toxicol Ind Health 1989;5:699 –730.

76. United States Food and Drug Administration. Indirect food additives, adjuvants, pro-duction aids, and sanitizers. Fed Regist 1998;63:35134 –5.

77. Pinkerton LE, Hein M, Stayner LT. Mortality among a cohort of garment workersexposed to formaldehyde: an update. Occup Environ Med 2004;61:193–200.

78. Coggon D, Harris EC, Poole J, Palmer KT. Extended follow-up of a cohort of Britishchemical workers exposed to formaldehyde. J Natl Cancer Inst 2003;95:1608 –15.

79. Block RM, Lewis RD, Sheats JB, Burke SG. Antibody formation to dog pulp tissuealtered by formocresol within the root canal. Oral Surg Oral Med Oral Pathol1978;45:282–92.

80. Rolling I, Thulin H. Allergy tests against formaldehyde, cresol, and eugenol in chil-dren with pulpotomized primary teeth. Scand J Dent Res 1976;84:345–7.

81. Pross HF, Day JH, Clark RH, Lees RE. Immunologic studies of subjects with asthmaexposed to formaldehyde and urea-formaldehyde foam insulation off products. Al-lergy Clin Immunol 1987;79:797– 810.

82. Doi S, Suzuki S, Morishita M, et al. The prevalence of IgE sensitization to formalde-hyde in asthmatic children. Allergy 2003;58:668 –71.

83. King SR, McWhorter AG, Seale NS. Concentration of formocresol used by pediatricdentists in primary tooth pulpotomy. Pediatr Dent 2002;24:157–9.

84. Nadin G, Goel B, Yeung C, Glenny A. Pulp treatment for extensive decay in primaryteeth. Cochrane Database Syst Rev 2003;1:CD003220.

85. Pumphreys RS. Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp2004;257:116 –28.

86. Darmani H, Al-Hiyasat A, Milhem M. Cytotoxicity of dental composites and theirleached components. Quintessence Int 2007;38:789 –95.

87. Rice H, Frush D, Farmer D, Waldhausen J. Review of radiation risks from computedtomography: essentials for the pediatric surgeon. J Pediatr Surg 2007;42:603–7.

Pulp Symposium


“New Age” Pulp Therapy: Personal Thoughtson a Hot DebatePaula Jane Waterhouse, BDS, PhD

AbstractThis article outlines the counterpoint delivered in the de-bate “Is Formocresol Obsolete?” It addresses the opinionsupporting the need to move away from formaldehyde-containing preparations in the dental care of children. Itis suggested that such a move should be made not justbecause of concerns relating to the possible toxicity offormaldehyde but to reflect a more contemporary, bi-ologic approach to pulp therapy in the primarydentition. (J Endod 2008;34:S47-S50)

Key WordsFormocresol, primary teeth, pulp therapy, pulpotomy

The debate over the use of formocresol solution and other formaldehyde-containingpreparations in children’s dentistry continues. This is welcomed and should be

regarded as a positive activity that will benefit ultimately those for whom we providedental care. Discussion at meetings and within peer-reviewed and non–peer-reviewedpublications has stimulated both specialist pediatric dentists and general dentists, notonly on both sides of the Atlantic but worldwide, to consider their stance over this issue.Should we, as providers of healthcare in the 21st century, continue to use formalde-hyde-containing medicaments in endodontic therapy?

This counterpoint will provide my personal thoughts on an undoubtedly contro-versial topic. These thoughts will be presented within the following sections:

● History: Where were we?● A perspective from the United Kingdom (UK) on formocresol preparations● Recent advances in primary tooth pulp biology● Formocresol: Saint or sinner?● Treatment● Evidence-based practice● The current UK guidelines.

History: Where Were We?Debate centered on clinical technique is not a product of modern medicine. The

varying treatments for the tooth pulp during the last 3 centuries illustrate this clearly.During the 1700s and early 1800s, metal foils were used to cap exposed pulp tissue (1),which would one use, gold or lead? Would you also prefer to cauterize the exposedtissue with a red-hot iron wire before placing the foil?

From the mid-1800s to the early 1900s, the use of medicaments in pulp therapiesemerged and involved wide-ranging substances such as asbestos fibers, cork, beeswax,pulverized glass, calcium compounds, and others based on eugenol. Interestingly, even at arelatively early time in medical and surgical knowledge, it is documented that there was greatdebate between those who believed a pulp was capable of healing and those who did not (2).

During this period of innovation and discovery, the first recorded use of a form-aldehyde-containing medicament was published. In 1874, Nitzel applied a tricresol-formalin tanning agent to 8000 exposed pulps (3). The technique appeared to beunpopular until Buckley’s method of treating putrescent pulps was published in 1904,suggesting the use of equal parts of tricresol and formalini (an aqueous solution offormaldehyde gas equivalent to 38% w/w formaldehyde).

In 1908, the use of a mummifying paste with a preparation including solid form-aldehyde was advocated (4). One year later, the International Dental Congress wasdevoted to the pulp and its treatment, and it was here that Boennecken (5) suggested hispreparation of 40% formalin, thymol, and cocaine to be superior to Buckley’s solutionin pulp amputation procedures.

By the late 1920s, there was disagreement between clinicians from Europe and theUnited States of America (USA) on treatment criteria and medicaments. In general,clinicians from Europe favored Gysi’s Triopaste with paraformaldehyde, and in the USA,pulp amputation was followed by application of Buckley’s formocresol solution (1).

In the middle of the last century there were many debates on the merits of differentmedicaments, and several variations of formocresol existed. The defining time forpulpotomy for the extensively carious primary tooth was the work published during aperiod of 25 years by Sweet (6, 7). During this time, multiple applications of Buckley’sformocresol were reduced to 2, and an additional application of formocresolized zinc

From the Department of Paediatric Dentistry, School ofDental Sciences, Newcastle University, Newcastle upon Tyne,United Kingdom.

Address requests for reprints to Dr Paula Jane Waterhouse,The School of Dental Sciences, Newcastle University, Fram-lington Place, Newcastle upon Tyne, NE2 4BW UK. E-mailaddress: [email protected].

Conflict of Interest: Paula Jane Waterhouse, BDS, PhD, hasresearch interests with Newcastle University through an inter-nal fund and also supervises several graduate students atNewcastle University. She is also a Council Member of theBritish Society of Paediatric Dentistry.0099-2399/$0 - see front matter



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oxide– eugenol cement was suggested. Since then, the technique for asingle visit, 5-minute application formocresol pulpotomy was devel-oped by using an as effective but weaker strength solution (8, 9). It wasreported that the formocresol addition to zinc oxide– eugenol cementcould be omitted (10).

It has been suggested that these later developments were driven bythe impetus from concerns regarding the safety of formocresol (1).

The UK Perspective on Formocresol PreparationsIn the UK, Buckley’s formocresol solution (38% w/w formalde-

hyde) and other formocresol preparations are not available for pur-chase on the general market. It is classed as a medicament, but it doesnot have a medicine license. It is prepared from its raw constituents inhospital-based pharmacy departments. In the late 1990s and early thiscentury fewer and fewer hospital pharmacists were willing to prepareBuckley’s formocresol solution, even in its diluted form.

Compounding this problem, there appears to have been confusionwithin pharmacy services when preparing the medicament in its diluteform (1). In particular, which formulation should be used to produce a1:5 dilution? This is reinforced by the Extra Pharmacopoeia stating that“. . . there is often confusion about the terminology and strength offormaldehyde” (1).

Buckley’s original formula appears to have contained 50% of a38% solution of formaldehyde (equivalent to 19% formaldehyde). InNewcastle, since 1979 the following formulation has been used: form-aldehyde solution BP (formalin), 19 mL; tricresol, 35 mL; glycerol, 15mL; and water to 100 mL. This contains 19% of a 38% solution offormaldehyde (equivalent to 7% formaldehyde) and is then diluted to a1:5; thus the final product contains 1/13 the concentration of formal-dehyde (gas). This is inarguably a small amount of formaldehyde.

The apparent confusion over its formulation might make compar-ison of studies problematic. Further uncertainty related to shelf life wasraised. “Laboratories making up these solutions have not only a certainreticence in handling these relatively toxic materials, but also have dif-ficulty in determining a shelf-life for the product” (1).

Full-strength Buckley’s formocresol solution is considered to havea shelf life of approximately 2 months if stored in brown glass bottles,but in its diluted form it is considered unstable and should be dilutedjust before use, which is impractical. Despite this, the use of pharmacy-diluted Buckley’s formocresol was effective, even under strict criteriafor success (11). I believe that in the UK the move away from Buckley’sformocresol has, in part, been driven by increasing difficulties in ob-taining the medicament and the increasing reticence of pharmacy staffto prepare the formulation (1, 12).

Recent Advances in Primary Tooth BiologyDental pulp is a richly innervated tissue, and recent research has

evaluated neuropeptide-containing nerve fibers. Nerves that expresssubstance P have provided insight into pulp nerve function. Studies haveshown that within a tooth the nerve fibers are predominantly nociceptive.These have an obvious pain receptive role, but they also play a primary rolein immunoregulation and healing (13). Both the permanent and primarydentitions show similar increases in innervation density with caries progres-sion, and Substance P is increased in painful caries cases.

In addition to this, during my own undergraduate days, despite fewpublished data, I was taught that in response to caries, primary toothpulps present a more pronounced and widespread inflammatory reac-tion compared with permanent teeth and might have been instrumentalin continuing with the amputation procedures (14). This response isrefuted by more recent immunohistochemical work that demonstratesequality between dentitions for the degree of vasodilation and angiogen-

esis in relation to caries insult, with responses predominantly in theregion of the pulp horns. Although primary teeth contain more immunecells in both intact and carious states, they appear to localize in amanner similar to permanent teeth (12).

It appears that the primary tooth pulp has good potential for tissuerepair and healing. In light of these contemporary findings, we as acollective professional body should be re-evaluating our approaches topulp therapy in the primary dentition as our colleagues within adultrestorative dentistry have already begun to do. We should be directingour research energies toward compiling a sound evidence base fortherapies that favor pulp regeneration.

Formocresol: Saint or Sinner?Despite formocresol’s undoubted clinical record of success and

its position as the gold standard medicament in both vital and nonvitalpulp therapy techniques in the primary dentition, in a recent Britishsurvey of 184 specialists in pediatric dentistry, 54% expressed concernover the safety of formocresol (15).

As clinicians, we all know from our own experience and from thereported literature that a pulpotomy performed with a 5-minute appli-cation of a 20% dilution of Buckley’s formocresol has a good prognosis,irrespective of whether the radicular pulp is viable. By virtue of theformaldehyde and cresol moieties, the solution has tissue fixative andantimicrobial properties and will fix and devitalize an irreversibly in-flamed radicular pulp.

I agree with other pediatric dentists in that the overall amount offormaldehyde in a working solution is small, but whether that amountmight cause problems should be explored further.

How many pulpotomies with formocresol would a child receive in1 visit? How many pulpotomies with formocresol might a pediatric den-tist undertake during the course of 1 day?

According to data sheets and a large base of published evidence foranimal and human studies, formaldehyde, a volatile organic compound,is toxic and corrosive, particularly local to the point of contact. Fewerfindings appear to be available for cresol, but it too is a known irritantand corrosive substance in its own right (16).

The UK’s Health and Safety Executive (HSE) presently rates expo-sure limits for formaldehyde for both long-term and short-term periodsin the workplace to be 2 ppm or 2.5 mg per cubic meter. There appearto be no data published related to the possible levels of formaldehydevapor and indeed cresol vapor in the dental working environment. Theamount of vapor exposure (ppm) to a child undergoing a formocresolpulpotomy is unknown, and the degree and potential effect of accumu-lative formaldehyde exposure to dental professionals are unknown.

In the UK in 2005, the HSE’s Working Group on Action to ControlChemicals (WATCH) published findings from an Advisory Committee onToxic Substances (ACTS) related to the carcinogenicity of formaldehyde(17). In Annex 2 of the report the toxicologic profile of formaldehyde isdiscussed, and in Annex 3 the carcinogenicity of formaldehyde is presentedby a summary of the human epidemiologic data mainly relied on by theInternational Agency for Research into Cancer (IARC) Working Group inreaching its conclusionrelating to formaldehydeexposureandcancer(18).

Formaldehyde is a known and accepted direct-acting irritant. Butwhat happens once it has contacted a tissue? This has been investigatedmainly in rats (which are obligate nasal breathers). Formaldehyde willpass into tissues such as mucous membranes rapidly, but uptake intoskin is poor. Once within tissues, formaldehyde will react directly withproteins and nucleic acids. To put this into the context of formocresol,tricresol is said to decrease the solubility and diffusion properties offormaldehyde, thus reducing movement out of the root canal (19).However, tricresol has been shown to increase the permeability of cell

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membranes by disrupting cell membranes’ lipid components (20). Dis-rupting cell membranes might potentiate further local toxic effects. Alter-natively, formaldehyde can enter a rapid metabolic pathway, convertingultimately to formate that is excreted in urine as formic acid, or entersnormal metabolic pathways, or is oxidized to carbon dioxide and exhaled(21–23). However, studies have shown that concentrations of 3 ppm form-aldehyde gas can saturate detoxification pathways in nasal epithelial cells,thus allowing “free” formaldehyde to cause damage locally (24).

Formaldehyde’s acute toxic effects are considered real and canoccur in humans from both the vapor and solution (25). In 2005, adental clinic in California was evacuated after spillage of a 1-ouncebottle of Buckley’s formocresol solution and was closed for the rest ofthe day. According to press reports, 10 people had difficulty breathingand required emergency room treatment (26).

Formaldehyde is an irritant to the eyes and respiratory tract inamounts as low as 0.1 ppm in some humans. Workers chronicallyexposed to mean levels of 0.2–2 ppm formaldehyde exhibited mildnasal epithelial lesions (loss of cilia, goblet cell hyperplasia, and milddysplasia) when compared with nonexposed controls (21).

Repeat dose inhalational studies with rodents and monkeys dem-onstrated that length of exposure and the concentration of formalde-hyde vapor (ppm) are related to the degree of histopathologicchange observed, ranging from slight hyperplasia to squamous cellmetaplasia of ciliated and non-ciliated respiratory epithelium. Thelevels that produced no observed adverse effect for long-term inha-lation studies with rodents were in the range of 1–2 ppm (21, 23).When formaldehyde was given to rats in drinking water, a 2-yearstudy showed local effects on gastric tissue, but no signs of systemictoxicity were reported (22, 25).

The WATCH group suggest that formaldehyde is toxic at the site ofinitial contact.

It is generally accepted that formaldehyde is genotoxic in vitro,inducing mutations and DNA damage in bacteria and in humans, mon-keys, and rodent cells (27–31).

Results from human and animal in vivo studies showed that find-ings indicate that formaldehyde acts as a mutagen at the site of contact(17). Formaldehyde has been shown to be an experimental animalcarcinogen in rats, producing nasal tumors at high levels of exposure(time and concentrations) (31). The carcinogenic potential of formal-dehyde is less evident in other rodents.

Nasal tumors in rats are thought to arise by a combination of severechronic local irritation and local genotoxicity. It is clearly stated byWATCH, “. . . By extrapolation, a combination of these circumstances inhumans would be of concern in relation to cancer” (17).

With respect to humans, many different regulatory authorities haveassessed the data published before 2004 (22, 23). Since the IARC find-ings, the HSE has appraised the epidemiologic studies consideredwithin the IARC report and stated that “sufficient evidence” exists thatformaldehyde has caused nasopharyngeal cancer in humans (32). TheHSE interpretation of the data from the studies considered is thatthey justify “increased concern” for the carcinogenic potential of

formaldehyde in humans, particularly in relation to nasopharyngealcancer, but that the data fall short of providing conclusive evidence.Doubts were raised concerning inconsistencies in some prominentnew studies (17).

In the context of formocresol vapor in a dental setting, what might thecombined effect of formaldehyde and cresol be? Would the added localtoxicity of cresol aid the local genotoxicity of formaldehyde? Are the levels ofthese substances so low in the air around a dental chair that this does notconstitute a risk? Clearly, these need further investigation with models thatreplicate the nasal and oral breathing patterns of humans.

TreatmentApplying formocresol to the radicular pulp of a cariously exposed

tooth will render the pulp in its most part nonvital. In many instancesdoes this relate to our present understanding of primary pulp biologyand pathophysiology? If one considers a carious exposure in a perma-nent tooth, it should be appreciated that much effort is directed atpreserving the pulp. Recent UK-based publications are beginning toreflect this approach for the primary dentition. On the basis of theclassification system of Ranly (33), the treatment of the extensivelycarious primary tooth can be divided into devitalization, preservation,and remineralization. The latter two are where we can move away fromformocresol and reflect a more modern, biologic approach to treat-ment, irrespective of whether formocresol is carcinogenic.

To present the alternatives that are presently clinically viable assuccinctly as possible, the techniques are tabulated by using a singleexample of related clinical research (Table 1).

With all the techniques/medicaments listed in Table 1 excludingindirect pulp therapy (IPT), care must be taken in assessing the status ofthe radicular pulp after coronal amputation. If the techniques are usedon healthy or reversibly inflamed pulp tissue, then a high degree ofsuccess has been recorded. These alternative techniques for vital pulptherapy might not provide such good success rates if used when radic-ular pulps are irreversibly inflamed. In such a situation other thanpulpectomy, there is not an equivalently successful pulpotomy medica-ment as formocresol solution (38, 39). I concur that it is in this areawhere formocresol, if removed completely, would be missed the mostand, in addition, for teeth exhibiting hyperalgesia or those without localanalgesia where in the past one would have used a paraformaldehydepreparation such as Miller’s paste to devitalize the tooth over time. If wewish to move away from such preparations, then treatment of such teethneeds further research and development.

IPT of symptom-free but extensively carious teeth shows greatpromise but should only be undertaken on teeth without signs of pulpaldegeneration. Not withstanding this, it is certainly an area worthy offurther study.

Evidence-based PracticeConsidering all the options we have, what works best? Unfortu-

nately, the Cochrane Systematic Review of pulp treatment for the exten-

TABLE 1. Overview of Some Alternatives to Formocresol for Vital Pulp Therapy

Material Clinical Success % Human ClinicalStudies

Tested AgainstFormocresol Effect (Animal Studies)

IPT 94% during period of mean 3.4 y (34) Yes Yes Preservation and remineralizationFerric sulphate 92% 4 y (35) Yes Yes PreservationMTA 100% 1 y (gray), 84.2% 1 y (white) (36) Yes Yes PreservationCalcium hydroxide 77.1% at 22.5 mo (11) Yes Yes Preservation and remineralizationLasers 100% 90 days (37) Yes Preservation

IPT, Indirect Pulp Therapy; MTA, Mineral Trioxide Aggregate; y, years; mo, months.

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sively decayed primary tooth showed a paucity of acceptable relatedclinical research but did draw conclusions, despite including only 3prospective randomized controlled trials (40). From the review it wasdemonstrated that formocresol, ferric sulfate, electrosurgical pulpot-omy, and zinc oxide– eugenol pulpectomy all performed equally well. Arecent meta-analysis of formocresol versus ferric sulfate found ferricsulfate to be as effective as formocresol (41).

The Current UK GuidelinesThe British Society of Paediatric Dentistry has produced a range of

clinical guidelines. The update reflects a shift in treatment modalitiesaway from formocresol, discussing IPT, vital pulpotomy, desensitizingpulpotomy, and pulpectomy (12). However, a 1:5 dilution of Buckley’sformocresol solution remains listed as a medicament within the guide-lines. This is an acknowledgment that the debate is far from over.

SummaryIn light of the findings presented, I would recommend that pedi-

atric dentists should be engaged in further good quality research anddebate relating to vital and nonvital pulp therapy for the primary denti-tion. This should include studies to increase our awareness of the pos-sible formaldehyde and cresol vapor exposure in the clinical environ-ment. In some instances, however, there might be difficulties obtainingethical approval for such work in certain countries.

At the beginning of this 21st century, we have greater understand-ing of the pulp biology, pathophysiology, and its powers of healing; weshould reflect this in our approach to clinical management and aim topreserve what pulp we can. This in itself might lead to a natural reduc-tion in the use of formocresol and herald a new age of pulp therapy.

AcknowledgmentsGrateful thanks to Professor Helen Rodd and Dr. Vidya Srini-

vasan for allowing use of their research and clinical materials.

References1. Nunn JH, Smeaton I, Gilroy J. The development of formocresol as a medicament for

primary molar pulpotomy procedures. J Dent Child 1996;63:51–3.2. Glass RL, Zander HA. Pulp healing. J Dent Res 1949;28:97–107.3. Schwartz EA. Formocresol vital pulpotomy on the permanent dentition. J Canad Dent

Assoc 1980;46:570 – 8.4. Bennette B. The preparation of mummifying paste. Br J Dent Sci 1908;51:02– 4.5. Boennecken H. Pulp amputation. Br Dent J 1909;30:1348 –9.6. Sweet CAJ. Procedure for treatment of exposed and pulpless deciduous teeth. J Am

Dent Assoc 1930;17:1150 –3.7. Sweet CAJ. Treatment of vital primary teeth with pulpal involvelment. J Col Dent Assoc

1955;33:381– 6.8. Straffon LH, Han SS. Effects of varying concentration of formocresol on RNA synthesis

of connective tissues in sponge implants. Oral Surg Oral Med Oral Pathol1970;29:915–25.

9. Morawa AP, Straffon LH, Han SS, Corpron RE. Clinical evaluation of pulpotomiesusing dilute formocresol. J Dent Child 1975;42:360 –3.

10. Beaver HA, Kopel HM, Sabes WR. The effect of zinc oxide-eugenol cement on aformocresolised pulp. J Dent Child 1966;33:381– 6.

11. Waterhouse PJ, Nunn JH, Whitworth JM. An investigation of the relative efficacy ofBuckley’s Formocresol and calcium hydroxide in primary molar vital pulp therapy.Br Dent J 2000;188:32– 6.

12. Rodd HD, Boissonade FM. Immunocytochemical investigation of immune cells withinhuman primary and permanent tooth pulp. Int J Paediatr Dent 2006;16:2–9.

13. Rodd HD, Boissonade FM. Substance P exposure in human tooth pulp in relation tocaries and pain experience. Eur J Oral Sc 2000;108:476 – 84.

14. Rayner J, Southam JC. Pulp changes in deciduous teeth associated with deep cariousdentine. J Dent 1979;7:39 – 42.

15. Hunter ML, Hunter B. Vital pulpotomy in the primary dentition: attitudes and prac-tices of Specialists in Paediatric Dentistry practising in the United Kingdom. Int JPaediatr Dentistry 2003;13:246 –50.

16. Physical and Theoretical Chemistry Laboratory, Oxford University, 2006. Available at:http://physchem.ox.ac.uk/MSDS/CR/cresol.html. Accessed August 15, 2007.

17. WATCH (2005). Working Group on Action to Control Chemicals. Committee paper2005/6. The carcinogenicity of formaldehyde. Available at: http://www.hse.gov.uk/aboutus/hsc/iacs/acts/watch/130105/p6.pdf. Accessed June 10, 2007.

18. International Agency for Research on Cancer. Monographs on the evaluation ofcarcinogenic risks to humans: volume 88: 2006; formaldehyde, 2-butoxyethanol and1-tert-butoxypropan-2-ol. Geneva, Switzerland: WHO.

19. ‘s Gravenmade EJ. Some biochemical considerations of fixation in endodontics. JEndod 1975;1:233–7.

20. Ranly DM, Lazzari EM. The formocresol pulpotomy: the past, the present, and thefuture. J Pedod 1978;2:115–27.

21. Agency for Toxic Substances and Disease Registry, Department of Health and HumanServices, 1999. Toxicological profile for formaldehyde. Available at: http://www.atsdr.cdc.gov.toxprofiles/tp111.html. Accessed June 10, 2007.

22. International Agency for Research on Cancer. Monographs on the evaluation ofcarcinogenic risks to humans: volume 62—wood dust and formaldehyde. Geneva,Switzerland, WHO, 1995.

23. HCN-DECOS (Health Council of the Netherlands-Dutch Expert Committee on Occu-pational Standards) 2003. Formaldehyde: health-based recommended occupationalexposure limit. Publication number 2003/020SH; The Hague.

24. Casanova M, Heck HAD. Further studies on the metabolic incorporation and covalentbonding of inhaled [3H] – and [14C] formaldehyde in Fischer-344 rats: effects ofglutathione depletion. Toxicol Appl Pharmacol 1987;89:105–21.

25. Organisation for Economic Cooperation and Development. SIDS Initial Assessment Report:2002. Available at: http://www.chem.unep.ch/irptc/sids/OECDSIDS/FORMALDEHYDE.pdf.Accessed August 14, 2007.

26. San Jose Mercury News 2005. Actual spill intrudes on medical center drill. Availableat: http://publicsafety.com/article/article.jsp?id�2460&siteSection�3. AccessedJune 3, 2007.

27. Wilkins FJ, Macleod HD. Formaldehyde induced DNA-protein crosslinks in Esche-richia coli. Mutat Res 1976;36:11– 6.

28. Orstavik D, Holgslo JK. Mutagenicity of endodontic sealers. Biomaterials1985;6:129 –32.

29. Goldmacher VS, Thilly WG. Formaldehyde is mutagenic for cultured human cells.Mutat Res 1983;116:417–22.

30. Nocentini S, Moreno G, Coppey J. Survival, DNA synthesis and ribosomal RNA tran-scription in monkey kidney cells treated by formaldehyde. Mutat Res1980;70:231– 40.

31. Swenberg JA, Kerns WD, Mitchell RI, Gralla EJ, Pavkov KL. Induction of squamous cellcarcinomas of the rat nasal cavity by inhalational exposure to formaldehyde vapor.Cancer Res 1980;40:3398 – 401.

32. International Agency for Research on Cancer. IARC classifies formaldehyde as car-cinogenic to humans. Press release no. 153, June 2004. Available at: http://www.iarc.fr/pageroot/PRELEASES/pr153a.html. Accessed August 20, 2004.

33. Ranly DM. Pulpotomy therapy in primary teeth: new modalities for old rationales.Pediatr Dent 1994;18:403–9.


35. Ibricevic H, Al-Jame Q. Ferric sulphate and formocresol in pulpotomy of primarymolars: long tern follow-up study. Eur J Paediatr Dent 2003;4:28 –32.

36. Agamy HA, Bakry NS, Mounir MMF, Avery DR. Comparison of mineral trioxide ag-gregate and formocresol pulp capping agents in pulpotomized primary teeth. PediatrDent 2004;26:302–9.

37. Elliott RD, Roberts MW, Burkes J, Phillips C. Evaluation of the carbon dioxide laser onvital human primary pulp tissue. Pediatr Dent 1999;21:327–31.

38. Patchett CL, Srinivasan V, Waterhouse PJ. Is there life after Buckley’s Formocresol?part 2: evelopment of a protocol for the management of extensive caries in theprimary molar. Int J Paediatr Dent 2006;17:199 –206.

39. Srinivasan V, Patchett CL, Waterhouse PJ. Is there life after Buckley’s Formocresol?part 1: a narrative review of the literature. Int J Paediatr Dentistry 2006;16:117–27.

40. Nadin G, Goel BR, Yeung CA, Gleny AM. Pulp treatment for extensive decay in primaryteeth. Cochrane Database Syst Rev 2003;1:CD003220.

41. Loh A, O’Hoy P, Tran X, et al. Evidence-based assessment: evaluation of formocresolversus ferric sulphate primary molar pulpotomy. PediatDent 2004;26:401–9.

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Regeneration Potential of the Young Permanent Tooth:What Does the Future Hold?Kenneth M. Hargreaves, DDS, PhD,* Todd Geisler, DDS,* Michael Henry, DDS, PhD,*and Yan Wang, DDS, PhD†

AbstractDuring the last 10–15 years, there has been a tremen-dous increase in our clinical “tools” (ie, materials,instruments, and medications) and knowledge from thetrauma and tissue engineering fields that can be ap-plied to regeneration of a functional pulp-dentin com-plex. In addition, recent case reports indicate that bi-ologically based endodontic therapies can result incontinued root development, increased dentinal wallthickness, and apical closure when treating cases ofnecrotic immature permanent teeth. The purpose of thisreview was to summarize these findings and illustratea path forward for the development and evaluation ofregenerative endodontic therapies. (J Endod 2008;34:S51-S56)

Key WordsEndodontics, pulp biology, regeneration, revasculariza-tion, tissue engineering

Treatment of the young permanent tooth with a necrotic root canal system and anincompletely developed root is fraught with difficulty. Not only is the root canal

system often difficult to fully debride, but the thin dentinal walls increase the risk of asubsequent fracture. Historically, acceptable endodontic results have been achievedthrough apexification procedures with use of long-term calcium hydroxide. Concernshave been raised, however, that long-term calcium hydroxide therapy might alter themechanical properties of dentin. Recent treatment strategies include 1-step creation ofan artificial apical barrier by using mineral trioxide aggregate (MTA) with or without anapical matrix followed by compaction of obturating material and placement of a coronalrestoration. MTA has been shown to produce good sealing effects under these condi-tions (1, 2). In addition, bonded composite resins have been reported to increasefracture resistance under some (3, 4) but not all experimental conditions (5). Unfor-tunately, even after treatment, these teeth have an elevated risk for fracture (6).

An alternative approach is to provide treatment under conditions where continueddentin formation is promoted. Several reports document that under conditions where atleast some pulp tissue appears vital, a pulp cap treatment permits continued dentinformation, described as either continued root development (maturogenesis) or apicalclosure (apexogenesis) (7). Although these findings and an emphasis for continuedresearch on vital pulp therapy are important (8), in many clinical cases the dental pulphas already undergone tissue necrosis before specialist consultation. Moreover, con-ventional endodontic therapy is not expected to result in continued dentin formation inthese circumstances. Thus, there is continued need to develop biologically based treat-ment regimens that offer the potential for continued hard tissue formation of the youngpermanent tooth with a necrotic root canal system and an incompletely developed root.

Regenerative Endodontic ProceduresSeveral groups recently have published preclinical research or case reports that

offer a biologically based alternative to conventional endodontic treatment of thesecomplex clinical cases. In general, these studies have evolved from the trauma litera-ture, where the following precepts have been established:

1. Revascularization occurs most predictably in teeth with open apices (9 –12).2. Instrumentation with NaOCl irrigation is not sufficient to reliably create the con-

ditions necessary for revascularization of the infected necrotic tooth (13).3. Placement of Ca(OH)2 in root canal systems prevents revascularization coronal

to the location of the Ca(OH)2 (14).4. The use of the “3 mix-MP” triple antibiotic paste, developed by Hoshino and

colleagues and consisting of ciprofloxacin, metronidazole, and minocycline, iseffective for disinfection of the infected necrotic tooth, setting the conditions forsubsequent revascularization (15–19).

This triple antibiotic mixture has high efficacy. In a recent preclinical study ondogs, the intracanal delivery of a 20-mg/mL solution of these 3 antibiotics via a Lentulospiral resulted in a greater than 99% reduction in mean colony-forming unit (CFU)levels, with approximately 75% of the root canal systems having no cultivable microor-ganisms present (19). Taken together, these studies provide a strong foundation levelof knowledge from the trauma literature that permits subsequent research to focus ondeveloping clinical methods for regeneration of a functional pulp-dentin complex.

From the *Department of Endodontics, University of TexasHealth Science Center, San Antonio, Texas; and †Departmentof Endodontics, School of Stomatology, Shandong University,Jinan, China.

Address requests for reprints to Dr K. M. Hargreaves,University of Texas Health Science Center, Mail Code 7982,7703 Floyd Curl Dr, San Antonio, TX 78229-3900. E-mailaddress: [email protected].

Conflicts of Interest: Kenneth M. Hargreaves, DDS, PhD, isa Grant Recipient from the National Institutes of Health and isthe Editor-in-Chief of the Journal of Endodontics. Todd Geisler,DDS, is a Grant Recipient from the AAE Foundation. MichaelHenry, DDS, PhD, is a Grant Recipient from the NationalInstitutes of Health. Yan Wang, DDS, PhD, reports no financialinterests or potential conflicts of interest.0099-2399/$0 - see front matter



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JOE — Volume 34, Number 7S, July 2008 Regeneration Potential of the Young Permanent Tooth S51

Although the trauma literature has used the term revasculariza-tion to describe this treatment’s outcome, the goal from an endodonticperspective is to regenerate a pulp-dentin complex that restores func-tional properties of this tissue, fosters continued root development forimmature teeth, and prevents or resolves apical periodontitis. Thus,using the term revascularization for regenerative endodontic proce-dures has been questioned (20). Therefore, this review will focus on theconcept of regenerating a functional pulp-dentin complex and will re-strict the use of the term revascularization to trauma studies.

It should be appreciated that research on regeneration of a pulp-dentin complex has a long history. For example, during the last 30 –50years, Nygaard-Østby and others have reported a series of preclinicalstudies and case studies on patients attempting to regenerate pulp-liketissue in teeth with either vital or nonvital diagnoses (21–24). Connec-tive tissue was demonstrated to grow as much as several millimeters intothe apical portion of the root canal system in teeth with necrotic pulpaldiagnoses (23). The results were variable, however, and histologicanalysis failed to reveal regeneration of a functional pulp-dentin com-plex. This lack of outcome is not surprising, however, given the level ofmaterials, instruments, and medications and the knowledge base avail-able at the time. Instead, current research in regenerative endodonticsuses greatly improved materials, instruments, and medications and ap-plies many principles from the fields of trauma research and tissueengineering (25–28).

In part on the basis of this expanding base of tools and knowledge,several recent case reports have been published describing regenerativeendodontic procedures applied to cases of necrotic immature perma-nent teeth. Key features of these published cases (20, 29 –32) are sum-marized in Table 1.

There are several common factors observed in these cases. First,although structurally weak, it is important to realize that the immaturepermanent tooth in general has a very wide apical opening that likely isconducive to tissue ingrowth. Second, these patients are young (8 –13years old), and several (33–37), but not all (38), studies suggest thatyounger ages have greater healing capacity or stem cell regenerativepotential. Third, none of the cases used instrumentation of the rootcanal walls, whereas all of the studies used NaOCl as an irrigant. Fourth,both Ca(OH)2 paste and combinations of multiple antibiotics have beenused in these patients. Outcome differences between these 2 medica-ments might reveal an important aspect of regenerative methods, be-cause many of the reported cases treated with Ca(OH)2 display intra-canal calcifications that appear to impede the continued thickening ofthe dentinal walls of these immature teeth (20). In addition, otherinvestigators (30) have suggested that the use of Ca(OH)2 might kill anyremaining pulpal cells, including stem or progenitor cells known to bepresent in dental pulp tissue (39 – 41), or possibly disrupt the apicalpapilla (30) and its resident stem cells (42, 43), which is critical forcontinued root development. Fifth, the formation of a blood clot mightserve as a protein scaffold, permitting 3-dimensional ingrowth of tissue.Sixth, nearly all of these studies report continued thickening of thedentinal walls and subsequent apical closure. It should be appreciated,however, that the radiographic finding of continued dentinal wall thick-ness does not address the cellular nature of this calcified material.

Largely on the basis of preclinical studies, it is possible that theradiographic presentation of increased dentinal wall thickness might bedue to ingrowth of cementum, bone, or a dentin-like material (23, 24,44 – 48). This diversity in cellular response is not surprising, given thathuman dental pulp cells can develop odontogenic/osteogenic, chon-drogenic, or adipogenic phenotypes, depending on their exposure todifferent cocktails of growth factors and morphogens (49, 50). Oneadvantage of case reports is that they are based on outcomes observedin actual patients and therefore might have great value in stimulating the

development of subsequent treatment methods; indeed, the discovery offluoride emerged from the keen observations of a practicing clinician.We now recognize, however, the critical importance of subjecting theseinitial findings to prospective randomized clinical trials to generateobjective measures of treatment efficacy and the potential liability foradverse events.

Thus, these and other case reports (51) should be viewed asgenerating a strong impetus for developing future prospective clinicaltrials. Taken together, these recent case studies support the hypothesisthat the immature necrotic permanent tooth might be particularly re-sponsive to biologically based endodontic therapies. Not only do thesetreatments provide an important alternative in a clinical situation withan otherwise poor prognosis, but equally important, these cases mightserve as an important clinical model to evaluate the application of tissueengineering concepts to the regeneration of a functional pulp-dentincomplex.

Application of Tissue Engineering Concepts toRegenerative Endodontics

The field of tissue engineering has literally exploded during the lastdecade, and extensive reviews on dental applications are available forthe interested reader (25, 26, 52–57). Here we briefly review 3 majorcomponents of tissue engineering from the concept of developing re-generative endodontic treatment regimens. Although basic research hasapplied nearly all of the tools of molecular biology for engineering ofdental tissues, including transfections and knockout animals, we willadopt a different perspective: What concepts of tissue engineering aremost likely to be available to clinicians when treating their patients withregenerative endodontic techniques? We have used this rather practicalperspective to shape our review of this field and to suggest a pathforward for developing and evaluating regenerative endodontics.

The first component of tissue engineering is a cell source. Odon-toblasts are of mesenchymal origin, and under appropriate conditions,cells from dental pulp, the apical papilla, and possibly other tissues canform odontoblast-like cells (49, 50, 56, 58 – 61). Controversies existamong several of these studies, because measuring only 1 or 2 charac-teristics of a cell might not be sufficient to conclusively determinewhether the resulting cell is a true odontoblast. Indeed, even amongodontoblasts, the phenotype varies in cells located in the apical versuscoronal dentin. Recent molecular studies have identified many of thegenes selectively expressed in odontoblasts (62, 63), however, and thisis likely to aid future studies characterizing the conditions necessary formesenchymal cells of multiple origins to differentiate into the odonto-blast phenotype. To date, the precise cell source(s) supporting thecontinued root development of the cases described in Table 1 are un-known. It is possible that: residual pulp cells might have remained vitalin some of the cases, cells from the apical papilla underwent prolifer-ation, or bleeding-induced angiogenesis might have recruited stem/progenitor cells from apical tissues including the apical papilla. Theclinical challenge will be to find a reliable cell source capable of differ-entiating into odontoblasts, convenient for harvesting, and autogenousto avoid tissue rejection or introduction of foreign pathogens (25).Moreover, a delivery method must be developed that permits controlledapplication of a known amount of cells into the apical region of the rootcanal system. Clearly, these are critical areas for future research.

The second component of tissue engineering is a physical scaffold.Tissues are 3-dimensional structures, and an appropriate scaffold isneeded to promote cell growth and differentiation. It is known thatextracellular matrix molecules control the differentiation of stem cells(64, 65), and an appropriate scaffold might selectively bind and localizecells (66), contain growth factors (67), and undergo biodegradation

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S52 Hargreaves et al. JOE — Volume 34, Number 7S, July 2008

TABLE 1. Key Features of Case Reports of Regenerative Endodontic Treatment Applied to Necrotic Immature Permanent Teeth

Toothno.

Patientage (y)

Patientsex

Preoperativepulpal

diagnosis

Preoperativeperiradicular

diagnosisTreatment1 Outcome Reference

no.

29 13 Female Necrosis Chronic apicalabscess

● 5 weekly visits, noinstrumentation, irrigationwith 5% NaOCl and 3%H2O2. Tooth left openbetween first and secondappointments to permitdrainage. Interappointmentmedicament: metronidazoleand ciprofloxacin.

● 6 weeks later: Broachprobed vital tissue in canal.Applied Ca(OH)2 paste, glassionomer cement, bondedcomposite resin.

● Sixth appointment: Vitaltissue observed 5 mmapical to canal orifice.

● 15 months: Positiveresponse to electricalpulp test.

● 30 months: Apicalclosure with thickeningof dentinal walls.

29

29 11 Male Necrosis Chronic apicalabscess

● First appointment: Rubberdam and access. Noinstrumentation. Deepirrigation with 10 mL 5.25%NaOCl and 0.12%chlorhexidine.Interappointmentmedicament: metronidazole,minocycline, andciprofloxacin (Lentulospiral). Cavit.

● 1 month: Irrigate 20 mL5.35% NaOCl. Bleedinginitiated with endo explorer.Stopped bleeding 3 mmfrom cementoenameljunction. MTA, wet pellet,Cavit.

● 2 weeks later: Compositerestoration.

● 26 days: Vital tissuepresent 15 mm intocanal system.

● 6–24 months: Gradualapical closure withthickening of dentinalwalls.

● Positive response topulpal cold test.

30

20 10 Female (Partial)pulpalnecrosis

Chronicperiradicularabscess

● First appointment: Rubberdam and access. Noinstrumentation. Irrigatewith 20 mL 2.5% NaOCl.Interappointmentmedicament: Ca(OH)2 paste.Caviton/IRM.

● 2 weeks later: Repeat.● 3 months: Replace Ca(OH)2● 11 months: Remove IRM and

replace with amalgam.

● 3 months: Found hardtissue at Ca(OH)2 site.Asymptomatic.

● 11 months: Thickeningof dentinal walls.

● 35 months: Continuedthickening of dentinalwalls and apical closure.

20

29 10 Male Necrosis Acuteperiradicularabscess

● First appointment: Rubberdam and access. Noinstrumentation. Irrigatewith 2.5% NaOCl.Interappointmentmedicament: Ca(OH)2 paste.

● 1 month: Irrigate with 2.5%NaOCl. Interappointmentmedicament: Ca(OH)2 paste.

● 2 months: Replace Ca(OH)2.● 7 months: Restore with

Caiton/Ketac Silver.

● 2 months: Found hardtissue at Ca(OH)2 site.Asymptomatic.

● 7 months: Apicalclosure, thickeningdentinal walls, calcifiedcoronal one third rootcanal system.

20

20 10 Female (Partial)pulpalnecrosis

Chronicperiradicularperiodontitis

● Formocresol pulpotomy.● 9 days: Rubber dam and

access. No instrumentation.Irrigate with 2.5% NaOCl.Interappointmentmedicament: Ca(OH)2 paste.

● 1 month: Replace Ca(OH)2.● 2 months later and every

2–3 months for 11 months:Replace Ca(OH)2.

● 18 months: Restore withamalgam.

● 1 month: Found hardtissue at mid-root.

● 11–54 months: Gradualapical closure,thickening dentinalwalls in apical half ofroot canal system.

20

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TABLE 1. (Continued)

Toothno.

Patientage (y)

Patientsex

Preoperativepulpal

diagnosis

Preoperativeperiradicular

diagnosisTreatment1 Outcome Reference

no.

29 9 Male Necrosis Chronicperiradicularperiodontitis

● Tooth left open for drainageat an emergency clinic.

● Rubber dam and access. Noinstrumentation. Irrigate 40mL 2.5% NaOCl.Interappointmentmedicament: Ca(OH)2 paste.

● 2 weeks and 5 weeks:Repeat.

● 5 months: Repeat.● 36 months: Restore with

amalgam to calcified bridge.

● 5 weeks: Hard tissuefound at mid-root.

● 5–60 months: Gradualdevelopment of rootlength, thickening ofdentinal walls, apicalclosure.

20

8 8 Male Necrosis Chronicperiradicularabscess

● First appointment:Consultation.

● Second appointment:Rubber dam and access. Noinstrumentation. Deepirrigation with 10 mL 5.25%NaOCl and 0.12%chlorhexidine.Interappointmentmedicament: metronidazole,minocycline, andciprofloxacin. Cavit.

● Third appointment: Irrigatewith 5.25% NaOCl, inducebleeding with endoexplorer. Cotton pelletplaced 3 mm belowcementoenamel junction for15-minute control locationof a blood clot. MTA, wetcotton pellet, Cavit.

● Fourth appointment:Remove Cavit and placebonded composite.

● 8 months:Asymptomatic. Apicalclosure with thickeningdentinal walls.

31

8 9 Male Necrotic Acute apicalabscess

● Trauma 2 years previouslytreated with Cvekpulpotomy procedure.

● Incision for drainage.● Disinfect tooth surface with

Betadine. Rubber dam andaccess. No instrumentation.Irrigate copiously with1.25% NaOCl.Interappointmentmedicament: metronidazole,minocycline, andciprofloxacin (Lentulospiral). IRM.

● 11 weeks: Irrigate with 10mL 1.25% NaOCl and 10 mLsterile water. Inducebleeding with endodonticfile inserted beyond theapex. 15 minutes allowedfor blood clot to reachcementoenamel junction.Place MTA over blood clotwith moist cotton pellet.Remove cotton pellet 1 hourlater and place bondedcomposite.

● 3 months:Asymptomatic. Diffuseradiopacities noted inroot canal system. Noresponse to pulp test(CO2 ice).

● 6–12 months:Asymptomatic. Diffuseradiopacities noted inroot canal system. Noresponse to pulp test(CO2 ice). Gradual apicaldevelopment andclosure.

32

IRM, intermediate restorative material; MTA, mineral trioxide aggregate.

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over time (68). Thus, a scaffold is far more than a simple lattice tocontain cells. From our perspective of focusing on practical clinicalapplications, we believe that platelet-rich plasma (PRP) satisfies manyof these criteria. PRP is autologous, fairly easy to prepare in a dentalsetting, rich in growth factors, degrades over time, and forms a 3-di-mensional fibrin matrix (69 –72). Interestingly, the case reports fromTable 1 all include formation of a blood clot. The use of PRP as analternative source for a fibrin clot might have several advantages, in-cluding increased concentration of growth factors and removal of eryth-rocytes that would be expected to undergo necrosis shortly after clotformation. To date, however, no publications have evaluated PRP forscaffold generation in regenerative endodontic applications. This andother potential scaffolds require future research.

The third component of tissue engineering to consider for regen-erative endodontics is signaling molecules. Both growth factors andother compounds are capable of stimulating cellular proliferation anddirecting cellular differentiation. As aforementioned, the observed ra-diographic thickening of the dentinal walls might be due to productionof cementum, bone, or dentin. It is likely that the cell source and theavailable signaling molecules play major roles in guiding the develop-ment of cells in the regenerating tissue. For example, the same culturesof human dental pulp cells can differentiate into cells resembling odon-toblasts/osteoblasts, adipoyctes, or chondrocytes, depending on thecombination of signaling molecules such as dexamethasone (49).Other investigators have shown that dentin or application of a dentinextract rich in growth factors will promote formation of an odontoblastphenotype (50, 62, 73). Extracts of dentin promote growth, becausemany growth factors are embedded into the dentin matrix during denti-nogenesis. Interestingly, ethylenediaminetetraacetic acid (EDTA) veryeffectively releases growth factors from human dentin (74). It is not yetknown, however, whether root canal irrigation with EDTA would pro-mote the development of odontoblast proliferation in a regenerativeendodontic procedure. It is likely that intracanal delivery of knownsignaling molecules or the solubilization of endogenous signaling mol-ecules will promote the formation of dentin in regenerative endodonticmethods.

A Path to the FutureCollectively, there has been a tremendous increase in our clinical

tools (ie, materials, instruments, and medications) and knowledgefrom the trauma and tissue engineering fields during the last decade.Moreover, recent case reports from multiple investigators support thefeasibility of developing biologically based regenerative endodonticprocedures designed to restore a functional pulp-dentin complex. Al-though these case reports primarily involve treating the immature per-manent tooth, it is quite possible that knowledge gained from this clin-ical application will have value in developing regenerative endodonticprocedures for the fully developed permanent tooth. In short, the ques-tion is no longer “can regenerative endodontic procedures be success-ful?” Instead, the important question facing us is “what are the issuesthat must be addressed to develop a safe, effective, and consistentmethod for regenerating a functional pulp-dentin complex in our pa-tients?”

In our opinion, the path to the future should focus on translationalresearch models that simulate likely clinical procedures. For example,although of clear scientific importance in understanding cellular mech-anisms, we do not believe that gene transfection is likely to have majorapplication in clinical endodontic procedures. Similarly, if natural toothdevelopment takes several years to occur, then we are not convincedthat the growth of artificial teeth with cells of allogenic or even xeon-genic origin (42, 75) is likely to have major clinical application. In-

stead, we believe that research modeling clinical procedures designedto regenerate a functional pulp-dentin complex is likely to have thegreatest impact. On the basis of current concepts, one approach wouldbe to focus on methods permitting the delivery of known cells, signalingmolecules, and a scaffold such as PRP into the apical 1–2 mm of a rootcanal system and then “backfilling” the root canal system with a solutionof PRP and signaling molecules. Because most cells must be less than 1mm away from a blood vessel to survive (76), research focusing on theinitiation of pulpal regeneration at the apex is likely to have majorimpact in developing other clinically useful procedures. Cellular prolif-eration could then occur along the backfill scaffold.

One possible approach is to develop a model system resemblingclinical application. For example, the revascularization of root canalsystems has been evaluated in human tooth slices after implantation intonude mice (who are immunocompromised, thus avoiding tissue rejec-tion) (77). Similarly, it might be possible to evaluate the initiation ofpulpal regeneration after various treatments by implanting the apical5–10 mm of sectioned human roots into nude mice. This approach hasparticular advantages, because it permits rapid evaluation of conditionsnecessary to initiate tissue regeneration and could be extended in futureresearch by evaluating conditions necessary to optimally disinfect ne-crotic root canal systems before tissue regeneration.

A recent editorial has suggested that “little progress has beenmade” in the years since the Nygaard-Østby studies on the regrowth ofdental pulp (8). From many perspectives, this statement is accurate. Webelieve, however, that the last decade has produced a critical mass ofknowledge and methods that are likely to result in the generation ofbiologically based endodontic therapies that will answer the challengeissued decades ago.

References1. Hachmeister DR, Schindler WG, Walker WA III, Thomas DD. The sealing ability and

retention characteristics of mineral trioxide aggregate in a model of apexification. JEndod 2002;28:386 –90.

2. Pace R, Giuliani V, Pini Prato L, Baccetti T, Pagavino G. Apical plug technique usingmineral trioxide aggregate: results from a case series. Int Endod J 2007;40:478 – 84.

3. Wilkinson KL, Beeson TJ, Kirkpatrick TC. Fracture resistance of simulated immatureteeth filled with resilon, gutta-percha, or composite. J Endod 2007;33:480 –3.


5. Stuart CH, Schwartz SA, Beeson TJ. Reinforcement of immature roots with a new resinfilling material. J Endod 2006;32:350 –3.

6. Cvek M. Prognosis of luxated nonvital maxillary incisors treated with calcium hy-droxide and filled with gutta-percha: a retrospective clinical study. Endod DentTraumatol 1992;8:45–55.

7. Weisleder R, Benitez CR. Maturogenesis: is it a new concept? J Endod2003;29:776 – 8.

8. Spangberg L. Who cares about the dental pulp? Oral Surg Oral Med Oral Pathol OralRadiol Endod 2007;104:587– 8.

9. Kling M, Cvek M, Mejare I. Rate and predictability of pulp revascularization in ther-apeutically reimplanted permanent incisors. Endod Dent Traumatol 1986;2:83–9.

10. Johnson WT, Goodrich JL, James GA. Replantation of avulsed teeth with immatureroot development. Oral Surg Oral Med Oral Pathol 1985;60:420 –7.

11. Laureys W, Beele H, Cornelissen R, Dermaut L. Revascularization after cryopreser-vation and autotransplantation of immature and mature apicoectomized teeth. Am JOrthod Dentofacial Orthop 2001;119:346 –52.

12. Andreasen JO, Borum MK, Jacobsen HL, Andreasen FM. Replantation of 400 avulsedpermanent incisors: 2—factors related to pulpal healing. Endod Dent Traumatol1995;11:59 – 68.

13. Cvek M, Nord CE, Hollender L. Antimicrobial effect of root canal debridement in teethwith immature root: a clinical and microbiologic study. Odontol Revy 1976;27:1–10.

14. Schroder U, Granath LE. Early reaction of intact human teeth to calcium hydroxidefollowing experimental pulpotomy and its significance to the development of hardtissue barrier. Odontol Revy 1971;22:379 –95.

15. Hoshino E, Kurihara-Ando N, Sato I, et al. In vitro antibacterial susceptibility ofbacteria taken from infected root dentine to a mixture of ciprofloxacin, metronida-zole, and minocycline. Int Endod J 1996;29:125–30.

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16. Sato T, Hoshino E, Uematsu H, Noda T. In vitro antimicrobial susceptibility to com-binations of drugs on bacteria from carious and endodontic lesions of human de-ciduous teeth. Oral Microbiol Immunol 1993;8:172– 6.

17. Sato I, Ando-Kurihara N, Kota K, Iwaku M, Hoshino E. Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole, andminocycline in situ. Int Endod J 1996;29:118 –24.

18. Takushige T, Cruz EV, Asgor Moral A, Hoshino E. Endodontic treatment of primaryteeth using a combination of antibacterial drugs. Int Endod J 2004;37:132– 8.

19. Windley W III, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immatureteeth with a triple antibiotic paste. J Endod 2005;31:439 – 43.

20. Chueh LH, Huang GT. Immature teeth with periradicular periodontitis or abscessundergoing apexogenesis: a paradigm shift. J Endod 2006;32:1205–13.

21. Nygaard-Ostby B, Hjortdal O. Tissue formation in the root canal following pulpremoval. Scand J Dent Res 1971;79:333– 49.

22. Horsted P, Nygaard-Ostby B. Tissue formation in the root canal after total pulpectomyand partial root filling. Oral Surg Oral Med Oral Pathol 1978;46:275– 82.

23. Nygaard-Østby B. The role of the blood clot in endodontic therapy: An experimentalhistologic study. Acta Odontol Scand 1961;19:323–53.

24. Nevins AJ, Finkelstein F, Borden BG, Laporta R. Revitalization of pulpless open apex teethin rhesus monkeys, using collagen-calcium phosphate gel. J Endod 1976;2:159–65.

25. Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: A review ofcurrent status and a call for action. J Endod 2007;33:377–90.

26. Nakashima M, Akamine A. The application of tissue engineering to regeneration ofpulp and dentin in endodontics. J Endod 2005;31:711– 8.

27. Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization ofimmature dog teeth with apical periodontitis. J Endod 2007;33:680 –9.

28. Flores MT, Andersson L, Andreasen JO, et al. Guidelines for the management of traumaticdental injuries: II—avulsion of permanent teeth. Dent Traumatol 2007;23:130–6.

29. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth withapical periodontitis and sinus tract. Dent Traumatol 2001;17:185–7.

30. Banchs F, Trope M. Revascularization of immature permanent teeth with apicalperiodontitis: new treatment protocol? J Endod 2004;30:196 –200.

31. Petrino JA. Revascularization of necrotic pulp of immature teeth with apical peri-odontitis. Northwest Dent 2007;86:33–5.

32. Thibodeau B, Trope M. Pulp revascularization of a necrotic infected immature per-manent tooth: case report and review of the literature. Pediatr Dent 2007;29:47–50.

33. Lei L, Liao W, Sheng P, Fu M, He A, Huang G. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture. SciChina 2007;50:320 – 8.

34. O’Driscoll SW, Saris DB, Ito Y, Fitzimmons JS. The chondrogenic potential of peri-osteum decreases with age. J Orthop Res 2001;19:95–103.

35. D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenicpotential of mesenchymal stromal stem cells from human vertebral bone marrow.J Bone Miner Res 1999;14:1115–22.

36. Amler MH. The age factor in human extraction wound healing. J Oral Surg1977;35:193–7.

37. Murray PE, Stanley HR, Matthews JB, Sloan AJ, Smith AJ. Age-related odontometricchanges of human teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod2002;93:474 – 82.

38. Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. Number and proliferativecapacity of osteogenic stem cells are maintained during aging and in patients withosteoporosis. J Bone Miner Res 2001;16:1120 –9.

39. Liu H, Gronthos S, Shi S. Dental pulp stem cells. Methods Enzymol 2006;419:99 –113.

40. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in humanbone marrow and dental pulp. J Bone Miner Res 2003;18:696 –704.

41. Gronthos S, Brahim J, Li W, et al. Stem cell properties of human dental pulp stemcells. J Dent Res 2002;81:531–5.

42. Sonoyama W, Liu Y, Fang D, et al. Mesenchymal stem cell-mediated functional toothregeneration in swine. PLoS ONE 2006;1:e79.

43. Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and itsresiding stem cells from human immature permanent teeth: a pilot study. J Endod2008;34:166 –71.

44. Ritter AL, Ritter AV, Murrah V, Sigurdsson A, Trope M. Pulp revascularization ofreplanted immature dog teeth after treatment with minocycline and doxycyclineassessed by laser Doppler flowmetry, radiography, and histology. Dent Traumatol2004;20:75– 84.

45. Nevins A, Finkelstein F, Laporta R, Borden BG. Induction of hard tissue into pulplessopen-apex teeth using collagen-calcium phosphate gel. J Endod 1978;4:76 – 81.

46. Skoglund A, Tronstad L. Pulpal changes in replanted and autotransplanted immatureteeth of dogs. J Endod 1981;7:309 –16.

47. Sheppard PR, Burich RL. Effects of extra-oral exposure and multiple avulsions onrevascularization of reimplanted teeth in dogs. J Dent Res 1980;59:140.

48. Kvinnsland I, Heyeraas KJ. Dentin and osteodentin matrix formation in apicoecto-mized replanted incisors in cats. Acta Odontol Scand 1989;47:41–52.

49. Wei X, Ling J, Wu L, Liu L, Xiao Y. Expression of mineralization markers in dental pulpcells. J Endod 2007;33:703– 8.

50. Huang GT, Shagramanova K, Chan SW. Formation of odontoblast-like cells fromcultured human dental pulp cells on dentin in vitro. J Endod 2006;32:1066 –73.

51. Shah N, Logani A. Evaluation of revascularization to induce apexification/apexogensisin infected, nonvital immature teeth (abstract). In: IFEA Meeting; August 2007; Van-couver, British Columbia, Canada.

52. Risbud MV, Shapiro IM. Stem cells in craniofacial and dental tissue engineering.Orthod Craniofac Res 2005;8:54 –9.

53. Rahaman MN, Mao JJ. Stem cell-based composite tissue constructs for regenerativemedicine. Biotechnol Bioeng 2005;91:261– 84.

54. Modino SA, Sharpe PT. Tissue engineering of teeth using adult stem cells. Arch OralBiol 2005;50:255– 8.

55. Feinberg SE, Aghaloo TL, Cunningham LL Jr. Role of tissue engineering in oral andmaxillofacial reconstruction: findings of the 2005 AAOMS Research Summit. J OralMaxillofac Surg 2005;63:1418 –25.

56. Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S. The efficacy of mesen-chymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res2005;8:191–9.

57. Sloan AJ, Smith AJ. Stem cells and the dental pulp: potential roles in dentine regen-eration and repair. Oral Dis 2007;13:151–7.

58. Zhang W, Walboomers XF, Wolke JG, Bian Z, Fan MW, Jansen JA. Differentiationability of rat postnatal dental pulp cells in vitro. Tissue Eng 2005;11:357– 68.

59. Alliot-Licht B, Bluteau G, Magne D, et al. Dexamethasone stimulates differentiation ofodontoblast-like cells in human dental pulp cultures. Cell Tissue Res 2005;321:391–400.

60. Kikuchi H, Suzuki K, Sakai N, Yamada S. Odontoblasts induced from mesenchymalcells of murine dental papillae in three-dimensional cell culture. Cell Tissue Res2004;317:173– 85.

61. Miura M, Gronthos S, Zhao M, et al. SHED: Stem cells from human exfoliated decid-uous teeth. Proc Natl Acad Sci U S A 2003;100:5807–12.

62. Liu J, Jin T, Chang S, Ritchie HH, Smith AJ, Clarkson BH. Matrix and TGF-beta-relatedgene expression during human dental pulp stem cell (DPSC) mineralization. In VitroCell Dev Bio 2007;43:120 – 8.

63. Paakkonen V, Vuoristo JT, Salo T, Tjaderhane L. Comparative gene expression profileanalysis between native human odontoblasts and pulp tissue. Int Endod J2008;41:117–27.

64. Bi Y, Ehirchiou D, Kilts TM, et al. Identification of tendon stem/progenitor cells andthe role of the extracellular matrix in their niche. Nature Med 2007;13:1219 –27.

65. Yamamura T. Differentiation of pulpal cells and inductive influences of various matriceswith reference to pulpal wound healing. J Dent Res 1985;64(Special issue):530–40.

66. Vacatello M, D’Auria G, Falcigno L, et al. Conformational analysis of heparin bindingpeptides. Biomaterials 2005;26:3207–14.

67. Yamada Y, Ueda M, Naiki T, Takahashi M, Hata K, Nagasaka T. Autogenous injectablebone for regeneration with mesenchymal stem cells and platelet-rich plasma: tissue-engineered bone regeneration. Tissue Eng 2004;10:955– 64.

68. Young CS, Terada S, Vacanti JP, Honda M, Bartlett JD, Yelick PC. Tissue engineeringof complex tooth structures on biodegradable polymer scaffolds. J Dent Res2002;81:695–700.

69. Ito K, Yamada Y, Nagasaka T, Baba S, Ueda M. Osteogenic potential of injectable tissue-engineered bone: a comparison among autogenous bone, bone substitute (Bio-oss),platelet-rich plasma, and tissue-engineered bone with respect to their mechanical prop-erties and histological findings. J Biomed Mater Res 2005;73A:63–72.

70. Anitua E, Andia I, Sanchez M, et al. Autologous preparations rich in growth factorspromote proliferation and induce VEGF and HGF production by human tendon cellsin culture. J Orthop Res 2005;23:281– 6.

71. Anitua E, Sanchez M, Nurden AT, Nurden P, Orive G, Andia I. New insights into and novelapplications for platelet-rich fibrin therapies. Trends Biotechnol 2006;24:227–34.

72. Ogino Y, Ayukawa Y, Kukita T, Koyano K. The contribution of platelet-derived growthfactor, transforming growth factor-beta 1, and insulin-like growth factor-I in platelet-rich plasma to the proliferation of osteoblast-like cells. Oral Surg Oral Med OralPathol Oral Radiol Endod 2006;101:724 –9.

73. Smith AJ. Vitality of the dentin-pulp complex in health and disease: growth factors askey mediators. J Dent Ed 2003;67:678 – 89.

74. Graham L, Cooper PR, Cassidy N, Nor JE, Sloan AJ, Smith AJ. The effect of calciumhydroxide on solubilization of bioactive dentine matrix components. Biomaterials2006;27:2865–73.

75. Sharpe PT, Young CS. Test-tube teeth. Sci Am 2005;293:34 – 41.76. Helmlinger G, Yuan F, Dellian M, Jain RK. Interstitial pH and pO2 gradients in solid

tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med1997;3:177– 82.

77. Goncalves SB, Dong Z, Bramante CM, Holland GR, Smith AJ, Nor JE. Tooth slice-basedmodels for the study of human dental pulp angiogenesis. J Endod 2007;33:811– 4.

Pulp Symposium


Contemporary Perspectives on Vital Pulp Therapy: ViewsFrom the Endodontists and Pediatric DentistsN. Sue Seale, DDS, MSD,* and Gerald N. Glickman, DDS, MS†

AbstractThe purpose of this study was to determine the level ofagreement between pediatric dentists and endodontistsat a pulp therapy symposium conjointly sponsored bythe American Association of Endodontists (AAE) andthe American Academy of Pediatric Dentistry (AAPD) onNovember 2–3, 2007. Presymposium and postsympo-sium tests were administered, and respondent answerswere compared between pediatric dentists and end-odontists. Opinions on 3 areas were sought: pulp ther-apy for cariously involved primary teeth; indirect pulptreatment (IPT) for cariously involved immature perma-nent teeth; and innovative treatment options includingpulpal revascularization and regeneration. Results wereanalyzed with �2 tests. Comparisons of presymposiumand postsymposium responses and between the 2groups of attendees indicated that the pediatric den-tistry and endodontic communities agree that formo-cresol will be replaced as a primary tooth pulpotomyagent, that mineral trioxide is the first choice to takeits place, that IPT in primary teeth holds hope as a re-placement for pulpotomy, and that IPT is an acceptablepulp therapy technique for cariously involved young per-manent teeth. Both groups believe that pulp revascu-larization and regeneration will be viable treatmentmodalities in the future. The AAE and the AAPD arepositioned to begin preparation of best practice guide-lines that share common language and treatment rec-ommendations for pulp therapies performed by bothspecialties. (J Endod 2008;34:S57-S61)

Key WordsIndirect pulp capping, pulp therapy, pulpotomy

This symposium was intended to bring together 2 different disciplines, pediatricdentistry and endodontics, to hear and evaluate the best evidence surrounding the

pulpal therapy treatments they commonly perform. One anticipated outcome of thesymposium was to begin preparation for working together to produce best practiceguidelines that share common language and treatment recommendations. Such anoutcome would require both disciplines to agree with interpretation of the evidencepresented concerning the shared treatments.

Because this was the first such endeavor to bring these 2 specialties together, it wasanticipated that there would be a diverse cross-section of opinions, both within eachindividual specialty and across the 2 specialties. Therefore, the planning committeesought to determine, through a brief pretest administered before the first speaker, thebaseline opinions of the attendees concerning the various topics to be presented.The planning committee also needed to determine what effect, if any, the conference pre-sentations had on attendees’ opinions, specifically regarding reaching agreements on theevidence presented to support the treatments being discussed. To that end, a morein-depth post-test was created and administered to the attendees via a real-time elec-tronic audience response system (ARS).

The purpose of this article was to present the results of the opinion surveys andreport the current status of agreement of the 2 specialties concerning the 3 major areasof interest: pulp therapy for the cariously involved primary tooth; indirect pulp treat-ment (IPT) for the cariously involved, immature permanent tooth; and innovative treat-ment options including pulpal revascularization and pulpal regeneration, both cur-rently under investigation.

MethodsAn 8-question pretest was prepared and administered to attendees before the first

presentation. The first 3 questions asked for demographic data, including dental dis-cipline, age, and current situation (pediatric or endodontic practitioner, pediatric orendodontic resident, or academician). Five additional questions used a 5-point Likertscale with the choices of strongly agree, agree, neutral, disagree, and strongly disagreeand queried about primary tooth pulpotomy and primary and permanent tooth IPT.Frequency tables of responses to the pretest questions were calculated for all respon-dents and compared by discipline, age group, and current career position by using �2

analysis, with a significance level of P � .05.After the last speaker, a more detailed set of 20 questions about the same topics

was presented to the audience for their opinion via an electronic ARS. The same 3demographic questions that were asked in the pretest were repeated, so that attendees’responses could be identified by discipline, age group, and current career position.Additional questions used the Likert scale or allowed the attendees to choose a singlebest answer from a list of options and patient scenarios. Six questions addressed pri-mary tooth pulpotomy, including medicament choice and opinions about formocresolas a primary tooth pulpotomy agent. Four questions asked for opinions about indirectpulp capping (IPC)/stepwise excavation in primary teeth, and an additional 5 questionsasked about the same procedure in permanent teeth. Five questions addressed pulpalrevascularization and the potential for stem cell research for pulpal regeneration.Frequency tables of responses to the ARS questions were calculated for all respondentsand compared by discipline (pediatric dentist or endodontist) by using �2 analysis, witha significance level of P � .05.

From the *Department of Pediatric Dentistry and †Depart-ment of Endodontics, Baylor College of Dentistry, Texas A&MUniversity Health Science Center, Dallas, Texas.

Address requests for reprints to Dr Seale at [email protected].

Conflict of Interest: N. Sue Seale, DDS, MSD, reports nofinancial interests or potential conflicts of interest. Gerald N.Glickman, DDS, MS, reports no financial interests or potentialconflicts of interests.0099-2399/$0 - see front matter



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JOE — Volume 34, Number 7S, July 2008 Contemporary Perspectives on Vital Pulp Therapy S57

ResultsA total of 376 individuals provided responses, and they were di-

vided as follows: 79 endodontists, 23 endodontic residents, 231 pedi-atric dentists, 21 pediatric dental residents, and 22 other. The numbersof residents and nonspecialists were small. Therefore, �2 analyses wereonly performed on responses from pediatric dentists and endodontists.

One of the major areas addressed by the speakers was pulp treat-ment for the cariously involved primary tooth. Issues covered includedthe controversy surrounding the use of formocresol as a pulpotomyagent in primary teeth and the level of evidence supporting either dis-continuing its use or maintaining it as a viable pulpotomy agent; thestatus of different pulpotomy agents for primary teeth and the level ofevidence that supports them; and the use of IPT as an alternative topulpotomy for cariously involved primary teeth.

Pretest responses concerning the acceptability of formocresol as acontemporary technique for primary tooth pulpotomy were significantlymore positive (P � .001) from pediatric dentists, with 80% agreeing orstrongly agreeing compared with only 29% of endodontists. Three of thepostseminar ARS questions revisited this issue, primarily concerningformocresol’s safety. When attendees were asked to respond to thestatement “formocresol, when used as a primary tooth pulpotomyagent, presents documented danger to the patient,” pediatric dentists(5%) were significantly (P � .001) less likely than endodontists (15%)to agree or strongly agree. When asked whether the fact that formocre-sol is a potential carcinogen should contraindicate its future usage inpediatric pulp therapy, however, 18% of pediatric dentists agreed orstrongly agreed, compared with 37% of endodontists. Again, these dif-ferences were significant (P � .001; Fig. 1). Attendees were asked theiropinion about the statement “formocresol will be replaced as a primarytooth pulpotomy agent, not because of its danger to patients, but be-cause there is much controversy about its potential to be dangerous.”Pediatric dentists and endodontists were unified in their opinions, with78% and 76%, respectively, agreeing or strongly agreeing.

Pulpotomy agents or treatment alternatives for cariously involvedprimary teeth were addressed in 2 post-symposium ARS questions. At-tendees were asked to give their opinions of the best treatment for areversibly inflamed primary molar with a large carious lesion encroach-ing on the pulp. They did this by choosing from a list that included an IPTor a pulpotomy with formocresol, ferric sulfate, mineral trioxide aggre-gate (MTA), or sodium hypochlorite. MTA was the favorite pulpotomyagent, chosen most often by both pediatric dentists (30%) and end-odontists (34%), whereas 20% of pediatric dentists and 4% of end-odontists chose formocresol. The second question dealt with choices of

agents for pulpotomy and asked, “If cost were not an issue, which is therecommended medicament for pulpotomies in primary teeth?” MTAwas the overwhelming winner, with pediatric dentists and endodontistsin agreement, choosing it 85% of the time. Only 15% of pediatric den-tists and 3% of endodontists chose formocresol (Fig. 2).

IPT in primary teeth was addressed in the pretest by asking attend-ees whether IPT was an acceptable substitute technique to replace pul-potomy to maintain vitality of cariously involved primary teeth. End-odontists were significantly (P � .003) more likely at 47% to agree orstrongly agree, compared with pediatric dentists (32%). The post-symposium ARS used 5 questions to further explore opinions of attend-ees concerning the subject of IPT in primary teeth. IPT was offered as atreatment option in cariously involved primary teeth in a question thatasked attendees to choose from a list the best treatment for a reversiblyinflamed primary molar with a large carious lesion encroaching on thepulp. Forty-seven percent of pediatric dentists and 58% of endodontistschose IPT (Fig. 3).

A second question asked attendees to respond to the statement“there is convincing evidence that IPT is as successful as a pulpotomy inprimary teeth with reversible pulpitis.” Seventy-four percent of pediatricdentists and 70% of endodontists agreed or strongly agreed. Whenasked to respond to the statement “there is convincing evidence thatprimary teeth with reversible pulpitis should all be treated by step-wiseexcavation for 3 months and only receive a pulpotomy if exposureoccurs on re-entry to remove remaining caries,” attendees were divided

5%

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37%

0% 10% 20% 30% 40%

Documenteddanger topatient

Fact that is acarcinogen

contraindictesits use

EndodonPed Den

% of respondents who agreed or strongly agreed (P<.001)

Figure 1. Comparison by specialty of responses to the statements: The fact thatformocresol is a potential carcinogen should contraindicate its future usage inpediatric pulp therapy; and when used as a primary tooth pulpotomy agent,formocresol presents a documented danger to the patient.

0% 20% 40% 60% 80% 100%

FeSO4

MTA

Formocresol

NaOCl

Chlorhexidine

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% of respondents who chose each treatment option

Figure 2. Comparison by specialty of responses to the question: If cost were notan issue, which is the recommended medicament for primary tooth pulpotomy?

20%4%

1%0

30%34%

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FeSO4pulpotomy

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IPC

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% of respondents who chose each treatment option

Figure 3. Comparison by specialty of responses to the question: Which is thebest treatment choice for a reversibly inflamed primary molar with a largecarious lesion encroaching on the pulp?

Pulp Symposium

S58 Seale and Glickman JOE — Volume 34, Number 7S, July 2008

in their opinions. Forty percent of pediatric dentists and 63% of end-odontists agreed or strongly agreed. A scenario question asked whatthey would do for a 5-year-old child with a second primary molar inwhich they had removed nearly all of the decay, knowing that if theyremoved the remaining decay, a pulp exposure would be imminent.More than half of the pediatric dentists (55%) and 71% of endodontistswould stop caries removal and do an IPT.

The final question about IPT in primary teeth in the post-symposium ARS asked attendees to choose from a list their main reasonfor not performing an IPT in a primary tooth with reversible pulpitis.The most frequently chosen answers in descending order by pediatricdentists were “pulpotomy is supported by evidence to have a better,more predictable outcome” (40%), “there is inadequate reimburse-ment by third party payers for the procedure” (32%), “there is insuffi-cient evidence to support its efficacy and success” (19%), and “I don’tbelieve IPT is successful in primary teeth” (9%). Endodontists hadslightly different rankings of their choices, with “there is inadequatereimbursement by third party payers for the procedure” (35%), “pul-potomy is supported by evidence to have a better, more predictableoutcome” (28%), “there is insufficient evidence to support its efficacyand success” (18%), and “I don’t believe IPT is successful in primaryteeth” (20%) (Fig. 4).

A second major area addressed by the speakers was managementof the carious lesion encroaching on the pulp of an immature perma-nent tooth, including those with an open apex. Two pretest questionsdealt with attendees’ opinions about IPT for these teeth. The first askedfor reactions to the statement “indirect pulp capping is an acceptablecontemporary technique for maintaining the vitality of asymptomatic,cariously involved young permanent teeth.” Pediatric dentists wereoverwhelmingly positive and significantly (P � .001) more likely at94% to agree or strongly agree, compared with endodontists (69%).

The second pretest question asked for reactions to the statement“symptoms of reversible pulpitis are contraindications to IPT in youngpermanent teeth.” Endodontists were significantly (P � .02) morelikely to agree or strongly agree at 31% than pediatric dentists at 26%.The post-symposium ARS used the exact same question to assess opin-ions after the presentations, and there was a significant difference inhow the attendees responded to this question by the end of the confer-ence. When the endodontists’ pretest responses (31%) were comparedwith their ARS responses, significantly fewer (P � .001) agreed orstrongly agreed (8%) that symptoms of reversible pulpitis were a con-traindication to IPT. The same trend was true for pediatric dentists, with

significantly fewer (P � .001) at 7% agreeing or strongly agreeing thatsymptoms of reversible pulpitis were a contraindication to IPT, com-pared with their pretest responses (26%) (Fig. 5).

Additional post-symposium ARS questions asked attendees’ opin-ions of the stepwise, 2-appointment version of IPT in permanent teeth.One question asked about agreement with “step-wise excavation as apractical treatment modality for IPT in young permanent teeth.” Pedi-atric dentists were significantly (P � .03) more likely to agree orstrongly agree at 71%, compared with 59% of endodontists. Anotherquestion asked attendees to choose from a list their main reason for notperforming stepwise excavation in a permanent tooth with an openapex. Pediatric dentists chose in descending order: patient compliancefor 2 appointments might be questionable (52%); MTA pulpotomy issupported by evidence to have a better outcome (20%); there is moreevidence to support the efficacy of the 1-step indirect pulp cap (18%);and inadequate reimbursement by third party payers for the procedure(10%). Endodontists expressed different preferences for their answers,with their first choice being: MTA pulpotomy is supported by evidence tohave a better outcome (61%); patient compliance for 2 appointmentsmight be questionable (27%); there is more evidence to support theefficacy of the one-step indirect pulp cap (6%); and inadequate reim-bursement by third party payers for the procedure (6%) (Fig. 6).

Finally, attendees were asked to choose from a list their strongestargument for performing stepwise caries excavation in a young perma-nent tooth. Responses from pediatric dentists included patient recall toassess symptoms and vitality (41%); patient recall to assess evidence ofroot maturation (31%); re-entry to ensure dentin remineralization

32%

35%

40%

28%

19%

18%

9%

20%

0% 10% 20% 30% 40%

Inadequatereimbursement

Pulpotomybetter

Insufficient IPCevidence

I don't believeIPC works inprimary teeth

EndodonPed Den

% of respondents who chose each option

Figure 4. Comparison by specialty of responses to the statement: My mainreason for not performing a pulpotomy in a primary tooth with reversiblepulpitis.

26%

31%

7%

8%

0% 10% 20% 30% 40%

Pre-symposium

ARS post-symposium

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% of respondents who agreed or strongly agreed

Figure 5. Comparison by specialty of presymposium and postsymposium re-sponses to statement: Symptoms of reversible pulpitis are contraindications toIPT in young permanent teeth with open apices.

52%

27%

10%

6%

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61%

48%

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0% 20% 40% 60% 80%

Questionable ptcompliance

Inadeqreimbursement

MTA pulp betterevidence

More evidencefor IPC

EndodonPed Den


Figure 6. Comparison by specialty of responses to the question: What is yourmain reason for not performing stepwise excavation in a permanent tooth withan open apex?

Pulp Symposium


(24%); and provides low-cost treatment for patients needing access tocare (4%). Endodontists responded differently, listing in order: patientrecall to assess evidence of root maturation (41%); patient recall toassess symptoms and vitality (25%); re-entry to ensure dentin reminer-alization (25%); payment to practitioner for a second appointment(6%); and provides low-cost treatment for patients needing access tocare (3%) (Fig. 7).

Root canal revascularization via blood clotting in necrotic youngteeth has been reported in the literature through documented casereports. A major aspect of this technique is usage of disinfecting irrig-ants such as sodium hypochlorite and chlorhexidine followed by theplacement of a special antibiotic mixture. Respondents’ opinions ex-pressed through the ARS indicated that the vast majority of pediatricdentists (87%) and endodontists (86%) agreed or strongly agreed thatthis will be a viable treatment modality for permanent teeth with apicalperiodontitis within the next 10 years. When asked to choose from a listtheir major concerns about the procedures, pediatric dentists gave thefollowing responses in descending order: no major concerns at thistime (34%); current evidence is based primarily on case reports(33%); unpredictability (18%); complex case selection criteria (13%);and use of antibiotic paste within the canal (2%). Endodontists gaveslightly different ordering to their choices: no major concerns at thistime (32%); unpredictability (26%); current evidence is based primar-ily on case reports (16%); use of antibiotic paste within the canal(14%); and complex case selection criteria (12%). The greatest dis-agreement between the 2 groups came when asked whether generaldentists should perform such procedures if properly educated andtrained. Pediatric dentists were favorably inclined, with 74% agreeing orstrongly agreeing compared with only 45% of endodontists.

Regeneration of pulp tissue involves tissue engineering therapiesby using stem cells, growth factors, and gene therapies. Although thisexciting concept is at its early stages of development, the AmericanAssociation of Endodontists has made regenerative endodontics andrevascularization high priority areas for further investigation. ARS ques-tions asked for opinions about whether, from a public health perspective,the future use of stem cells for pulp regeneration in permanent teeth wouldbe an acceptable treatment. Endodontists were more likely to agree orstrongly agree at 64%, compared with pediatric dentists at 37%. Thisquestion had the highest percentage of uncommitted responders, with33% of pediatric dentists and 21% of endodontists choosing neutral asa response. Finally, the ARS asked for opinions from an ethical stand-

point whether they believed the future use of stem cells for pulp regen-eration in permanent teeth would be an acceptable treatment. All of theendodontists (100%) and 96% of pediatric dentists agreed or stronglyagreed.

DiscussionEvidence of a merging level of agreement between pediatric den-

tists and endodontists concerning important issues addressed by thepresenters was needed for the symposium planning committee’s goal tobe met for the collaborative production of pulp therapy guidelines.

Pretest responses indicated significant differences in opinions be-tween pediatric dentists and endodontists concerning the acceptabilityof most of the pulp therapy treatments under consideration. Beginningwith primary tooth pulpotomy agents and formocresol in particular, thevast majority of pediatric dentists initially viewed formocresol pulpot-omy as an acceptable pulp treatment for cariously involved primaryteeth. Although the pretest question did not ask respondents to chooseformocresol from among other pulpotomy agents, as did the ARS ques-tions, 80% of the pediatric dentists favored its use at that point. Com-paring the large number of positive responses initially to formocresolwith the ARS responses appears to indicate a changing attitude by pedi-atric dentists. In the post-symposium ARS questions, only 20% choseformocresol as the best treatment for a primary tooth with reversiblepulpitis, and only 15% chose it as the recommended medicament forprimary tooth pulpotomy. The way the questions were phrased does notallow direct comparisons between presymposium and postsymposiumresponses, but these results certainly appear to suggest that formocresollost popularity. The trend away from formocresol would place pediatricdentists more in agreement with endodontists, who did not favor for-mocresol either pre- or post-symposium.

There was a different trend apparent when pediatric dentists wereasked to comment on the safety of formocresol. Their responses to ARSquestions about its documented danger to the patient and whether itspotential as a carcinogen should contraindicate its use indicated thatthey do not believe the case that formocresol is dangerous has beenmade; only 5% of pediatric dentists and 18% of endodontists agreed.They did appear convinced, however, that it will be replaced because itis too controversial. In that respect, they were in complete agreementwith the endodontists. When applying these data to the production ofpractice guidelines, it is probably most important that the 2 groups betogether in their opinions about the need to find and endorse a replace-ment for formocresol.

Continuing with the issue of primary tooth pulp therapy and withrespect to agents used for pulpotomy, post-symposium ARS data indi-cated that pediatric dentists and endodontists are unified in their over-whelming favor of MTA as the pulpotomy agent of choice. This finding isinteresting in light of the fact that there are few well-designed studiesexamining MTA as a primary tooth pulpotomy agent, even though thosestudies that are available report positive outcomes in favor of MTA. Asecond option being examined to replace formocresol pulpotomy as thetreatment of choice for cariously involved primary teeth is IPT. Pretestdata indicated poor acceptance by the pediatric dentistry respondents,with less than one third agreeing that it was an acceptable substitutetechnique for pulpotomy. Their post-symposium ARS responses ap-peared to indicate a marked trend toward a more positive attitude aboutIPT for primary teeth. More than half would stop caries excavation andperform an IPT rather than a pulpotomy, and 75% agreed that there isevidence that IPT is as successful as pulpotomy in primary teeth. End-odontists started out more positively than pediatric dentists about theprocedure for primary teeth and remained that way. The gap between

24%

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Re-entry fordentin remin

Pt recall forsymptoms &

vitality

Pt recall/rootmaturation

Payment for2nd visit

Low costTx/Access to

care

EndodonPed Den


Figure 7. Comparison by specialty of responses to the question: Which of thefollowing would be your strongest argument for performing stepwise cariesexcavation in young permanent teeth?

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S60 Seale and Glickman JOE — Volume 34, Number 7S, July 2008

them narrowed, however, as pediatric dentists more frequently ex-pressed positive opinions in their responses after the symposium.

The issue where pediatric dentists and endodontists have the mostpotential to both be treating the same kinds of teeth is the managementof cariously involved young permanent teeth with immature or openapices. This is also the issue where there has previously been the mostdivergence of opinion between the 2 groups concerning the appropri-ateness of IPT for these teeth. The pretest question responses bore outthis divergence. Almost all of the pediatric dentists (94%) opined thatIPT was an acceptable technique for the “asymptomatic cariously in-volved young permanent tooth,” compared with only approximately twothirds of the endodontists.

Most pediatric dentists and endodontists, however, agreed to apretest question concerning reversible symptoms of pulpitis contrain-dicating IPT. By the end of the conference, their opinions about whethersuch symptoms were a contraindication to IPT changed dramatically.The post-symposium ARS question was worded exactly the same way asin the pretest. Only 8% of endodontists and 7% of pediatric dentistsagreed that symptoms of reversible pulpitis were a contraindication toIPT, indicating agreement on this important diagnostic issue.

The IPT procedure in permanent teeth presented at the symposiumwas the variant called stepwise excavation. The variant involves 2 ap-pointments and aims to eventually remove all affected dentin rather thanleave a small amount in the tooth as is performed in the 1-appointmentIPT. The procedure has not received wide exposure in the United Statesbecause most of the publications on its use and success have appearedin journals not widely read by the practicing community. The post-symposium ARS questions dealt mainly with the stepwise excavationversion of IPT and appeared to indicate similar favorable agreement onits use in permanent teeth by both pediatric dentists and endodontists.

It is this topic of the more conservative, cost-effective treatmentmodality of IPT for cariously involved young permanent teeth that is themost important issue for which the 2 communities must reach agree-ment and formulate practice guidelines with common language andintent. Many children and young adults who have the highest risk forcaries and lesions and who are candidates for IPT have either no payersources or sources with limited participation by individuals who per-form endodontic treatment (general dentists and endodontists). In fact,many cariously involved teeth in these young individuals have openapices and are simply not candidates for complete endodontic treat-ment. They need to be treated with the more complex and lengthyprocedure of vital pulpotomy to obtain root closure followed by com-plete root canal treatment. The length of time involved in completing the2 procedures might make them impractical for patients on some pay-ment programs such as Medicaid, where their eligibility might varyduring the time period required. The issue of access to care mandatesthat the 2 groups be unified in agreeing that IPT is an evidence-basedand appropriate pulp therapy modality for young permanent teeth withimmature or open apices.

ConclusionsIn summary, what do endodontists and pediatric dentists agree on?

These survey data appear to indicate that the pediatric dentistry andendodontic communities alike agree that formocresol will be replacedas a primary tooth pulpotomy agent, that MTA is the overwhelming firstchoice to take its place, that IPT in primary teeth holds hope as areplacement for pulpotomy, and that IPT is an acceptable pulp therapytechnique for cariously involved young permanent teeth with open api-ces. In addition, both the endodontists and pediatric dentists believe thatpulp revascularization and regeneration will be potentially new excitingtreatment modalities in the near future.

Pulp Symposium


journal of endodontics

Health & Medicine